Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure
Open accessAbstract
The dark side of melanin exposed: Sun worshippers may have more to worry about than the DNA damage that occurs while they're relaxing on the beach. It seems that the DNA photoproducts responsible for cancer-causing mutations in skin cells continue to be generated for hours after sunlight exposure. Premi et al. find that a key mediator of this delayed damage is melanin, a pigment thought to protect against cancer (see the Perspective by Taylor). They propose a “chemiexcitation” model in which reactive oxygen and nitrogen species induced by ultraviolet light excite an electron in melanin fragments. This energy is then transferred to DNA, inducing the same damage as ultraviolet light, but in the dark. Conceivably, this energy could be dissipated by adding quenchers to sunscreens. Science , this issue p. 842 ; see also p. 824
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Claims the paper makes
11 of 45 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured
- Interpretationcitation
The melanin requirement for nuclear nitration suggests that the nitric oxide requirement in melanocytes differs from that in cultured keratinocytes.
“The melanin requirement suggests that the NO• requirement in melanocytes is distinct from that observed in cultured keratinocytes (18).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [18] source
The Discussion (page unavailable) describes UVA-induced reactive oxygen species in keratinocytes as arising primarily through Nox1-based NADPH oxidase. It does not address a nitric oxide requirement in keratinocytes or compare one with melanocytes; searches for nitric oxide, NO synthase, and nitration found no passage supporting that comparison. (LLM, conf=0.75)
Experimental — accuracy not yet measured
- Premisecitation
Braf-mutant mice carrying the pheomelanin-associated Mc1re/e allele develop 10 times more spontaneous melanomas.
“Braf-mutant mice develop 10 times more spontaneous melanomas if they carry the pheomelanin-associated Mc1re/e allele (4).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [4] source
The paper’s results passage (labelled Abstract; page unavailable) reports that red Mc1re/e Braf-mutant mice developed melanomas without UV exposure at a higher rate than black Braf-mutant mice, with more than 50% of red mice having tumors after one year. Our copy does not give a tenfold comparison, so the precise magnitude attributed to the paper is not supported. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Interpretationreasoning
The double nature of melanin would explain the apparent cancer-facilitating effects of melanin seen in mice and human epidemiology.
“This double nature would explain the apparent cancer-facilitating effects of melanin seen in mice and in human epidemiology (2-4, 6).”
Quote in the paperSubstantial claim3 of 4 sources checked- cites [2] source
- cites [3] source
- cites [4] source
- cites [6] source
The Discussion (page unavailable) describes a balance between melanin’s protection and photosensitizing damage, and suggests photosensitization may contribute to the elevated skin-cancer risk associated with red or blonde hair. It also proposes that melanin-related cell death could favor expansion of mutant cells. The paper does not report cancer-facilitating effects of melanin in mice; its mouse experiments measured UV-induced cell death, not cancer. (LLM, conf=0.82)
Experimental — accuracy not yet measured
- Premisecitation
Most mutations in human melanomas show the UV signature of C→T substitutions at adjacent pyrimidines.
“Yet melanin's ROS generating properties do not explain its role in melanoma development because most mutations in human melanomas display the UV signature of C →T substitutions at sites of adjacent pyrimidines (8, 9).”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [8] source
The Introduction and “Canonical Mutations vs Signature Mutations” section report a preponderance of UV-signature mutations in melanomas from sun-exposed body sites. The claim omits that restriction and extends the finding to human melanomas generally. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [9] source
The Results (Landscape of nonsynonymous somatic mutations; page unavailable) report an excess of UV-linked C>T mutations at dipyrimidines in sun-exposed melanomas. The Discussion says the UV signature was not detected in acral, mucosal, or ocular melanomas. Thus the source supports the signature in sun-exposed melanomas, but not the claim as stated for human melanomas generally. (LLM, conf=0.85)
Experimental — accuracy not yet measured
- Premisecitation
UVA-irradiated mice do not develop melanoma if they lack melanin.
“UVA-irradiated mice do not develop melanoma if they lack melanin (3)”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [3] source
- Findingown data
Inducing lipid peroxidation in isolated nuclei with cumene hydroperoxide did not appear to induce CPD in nuclear DNA.
“A O2•–-initiated radical chain reaction in lipids was one possible conduit (26), but inducing lipid peroxidation in isolated nuclei using cumene hydroperoxide did not appear to induce CPD in nuclear DNA (fig. S3).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] source
- Findingown data
In murine melanocytes that contain melanin, CPD continue to be produced for at least three hours after UVA exposure ends, until DNA repair offsets the increase.
“Unexpectedly, melanin-containing murine melanocytes instead continued to generate CPD for at least three hours after UVA exposure, at which point generation was offset by DNA repair (Fig. 1B,C).”
Quote in the paperSubstantial claim - Findingown data
In melanin-containing cells, the (TC+CT)/TT ratio increased from 0.37 at 0 h to 1.33 during the following 2 h, with p = 0.027.
“The (TC + CT)/TT ratio in melanin-containing cells increased from the UVA-like 0.37 at 0 h (directly-induced CPD) to 1.33 in the CPD arising during the following 2 h (p = 0.027), a ratio more typical of cells irradiated with the higher-energy UVB.”
Quote in the paperSubstantial claim - Findingown data
Inhibiting iNOS with aminoguanidine completely suppressed dark CPD production.
“To determine if NO• is required for production of dark CPD, we inhibited iNOS by treating melanocytes with aminoguanidine. This resulted in complete suppression of dark CPD production (Fig. 3C).”
Quote in the paperSubstantial claim - Findingown data
UVA exposure of melanin-containing melanocytes created as much nuclear and cytoplasmic nitrotyrosine in 30 minutes as basal induction over about 8 days.
“In support of an additional UV role, we found that exposing melanin-containing melanocytes to UVA created as much nuclear and cytoplasmic nitrotyrosine in 30 min as had accumulated from basal induction over ~8 days (Fig. 3D,E) (fig. S2D) (see Methods).”
Quote in the paperSubstantial claim - Findingown data
In fibroblasts and albino murine melanocytes, CPD induction peaks immediately after UVA exposure and then declines through slow nucleotide excision repair.
“Consistent with this, we found that for fibroblasts and for melanocytes derived from albino mice, the peak of CPD induction was reached immediately upon exposure, followed by slow nucleotide excision repair (Fig. 1A) (fig. S1A). (14).”
Quote in the paperNot a substantial claim - Findingown data
In human melanocytes with modest CPD decline and no obvious dark CPD, siRNA knockdown of XPA or XPC revealed dark CPD.
“For human melanocytes in which there was a modest rate of CPD decline after exposure but which showed no obvious dark CPD, the dark CPD were revealed by siRNA knockdown of XPA or XPC transcripts (Fig. 1F).”
Quote in the paperSubstantial claim - Findingown data
Mass spectrometry showed that delayed CPD in melanin-containing murine melanocytes include cytosine-containing CPD that generate UV-signature C→T mutations.
“This analysis revealed that the delayed CPD in melanin-containing melanocytes included the cytosine-containing CPD that generate UV-signature C→T mutations (Fig. 2A,B).”
Quote in the paperSubstantial claim - Findingown data
In K14-Kitl mice homozygous for inactive Mc1re/e, which synthesize pheomelanin, both initial and dark CPD were twice as frequent as in black mice.
“Furthermore, in K14-Kitl mice homozygous for the inactive Mc1re/e allele, in which melanocytes synthesize red-yellow pheomelanin, both initial and dark CPD were twice as frequent as in black mice.”
Quote in the paperSubstantial claim - Findingown data
The NOX inhibitor VAS2870 abolished dark CPD production.
“The NOX inhibitor VAS2870 also abolished production of dark CPD (Fig. 3B).”
Quote in the paperSubstantial claim - Findingown data
After UVB, most CPD in melanocytes were formed in the dark even without repair knockdown.
“For the higher-energy UVB, the majority of CPD in melanocytes were created in the dark even without repair knockdown (figs. S1E-H).”
Quote in the paperSubstantial claim - Findingown data
Knockdown of Xpa or Xpc showed that dark CPD made up half of the total CPD in melanocytes.
“Knocking down excision repair of CPD using siRNA against Xpa or Xpc transcripts (corresponding to genes mutated in xeroderma pigmentosum) revealed that dark CPD constituted half of the total CPD (Fig. 1D).”
Quote in the paperSubstantial claim - Findingown data
Ethyl sorbate, a triplet-state quencher, prevented dark CPD production in intact melanocytes after UVA.
“To test whether this triplet state is required for dark CPD, we added ethyl sorbate, a specific quencher of triplet states (26), to intact melanocytes after UVA exposure. We found that this treatment prevented production of dark CPD (Fig. 3H).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] source
- Findingown data
The ratio of (TC+CT)/TT CPD was four-fold higher in delayed CPD than in directly induced CPD.
“Unexpectedly we observed a 4-fold higher ratio of (TC + CT)/TT CPD in the delayed CPD compared to directly-induced CPD, which is suggestive of unusual chemistry.”
Quote in the paperSubstantial claim - Findingown data
Kojic acid, an inhibitor of tyrosinase, suppressed dark CPD production by 85%.
“We found that kojic acid, an inhibitor of tyrosinase, the rate-limiting enzyme in melanin synthesis, suppressed production of dark CPD by 85% (Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
The delayed CPD after UVA in melanocytes are located in nuclear DNA.
“This result also indicated that delayed CPD resided in nuclear DNA.”
Quote in the paperSubstantial claim - Findingown data
In K14-Kitl mice after UVA, epidermal CPD at 2 hours was three times greater than immediately after exposure.
“After exposure of these mice to UVA, the level of epidermal CPD at the 2 hour timepoint was 3 times greater than it was immediately after exposure (Fig. 1G,H).”
Quote in the paperSubstantial claim - Findingown data
Scavenging superoxide with TEMPOL abolished dark CPD production after UVA.
“Because melanin generates superoxide radical ion (O2•–) while it is being irradiated, we specifically scavenged it with TEMPOL and found that this also abolished the production of dark CPD after UVA (fig. S2C).”
Quote in the paperSubstantial claim - Findingown data
CPD were generated without any UV when plasmid DNA and peroxynitrite were incubated with melanin, DHICA, or 5SCD.
“Importantly, we found that CPD were generated in the complete absence of UV when we incubated plasmid DNA and peroxynitrite with melanin, DHICA, or 5SCD (Fig. 4B).”
Quote in the paperSubstantial claim - Findingown data
The level of CPD induced without UV was approximately equal to that generated in pure DNA by 25 kJ/m2 UVA, about one-quarter of the minimal erythema dose.
“The level of CPD induced in the absence of UV was approximately equal to that generated in pure DNA by 25 kJ/m2 of UVA, an exposure about one-quarter of that required to produce a barely-perceptible sunburn (the “minimal erythema dose”).”
Quote in the paperSubstantial claim - Findingown data
CPD created by oxidizing melanin or its monomers included mutagenic cytosine-containing CPD.
“The CPD created by oxidizing melanin or its monomers included the mutagenic cytosine-containing CPD (fig. S4D).”
Quote in the paperSubstantial claim - Findingown data
Fragmentation of the HPLC fractions generated m/z peaks assignable to oxidation products of structure 1 or structure 2.
“Fragmention of these HPLC fractions generated m/z peaks assignable to oxidation products of either structure 1 or 2 created by known oxidation reactions.”
Quote in the paperSubstantial claim - Findingown data
HPLC separation and mass spectrometry of DHICA oxidation products revealed a single peak eluting in the highly polar region of the buffer gradient.
“When we separated reaction products by HPLC and scanned the HPLC eluate by mass spectrometry in negative ion mode for the corresponding 224 m/z product, we observed a single peak eluting in the highly polar region of the buffer gradient (Fig. 4E).”
Quote in the paperSubstantial claim - Findingown data
Synthetic melanin oxidized with peroxynitrite and incubated with DBAS generated chemiluminescence 100-fold larger than that seen in melanocytes.
“Synthetic melanin oxidized with peroxynitrite and incubated with DBAS generated a chemiluminescence signal 100-fold larger than seen in melanocytes (Fig. 4A)(fig. S4A).”
Quote in the paperSubstantial claim - Findingown data
In cell-free experiments, melanin polymer was rapidly solubilized after exposure to UVA or peroxynitrite.
“Cell-free experiments revealed that melanin polymer was rapidly solubilized after exposure to UVA or peroxynitrite (Fig. 4D).”
Quote in the paperSubstantial claim - Findingown data
After UVA exposure, 3D images reconstructed from serial planar images revealed granules inside the nucleus.
“After UVA exposure, 3D images reconstructed from serial planar images revealed granules inside the nucleus (Supplementary Movies S1 and S2).”
Quote in the paperSubstantial claim - Findingown data
Oxidizing synthetic melanin with horseradish peroxidase and hydrogen peroxide produced chemiluminescence at levels similar to peroxynitrite oxidation.
“To further test melanin's ability to host a triplet state, we oxidized synthetic melanin with horseradish peroxidase in the presence of hydrogen peroxide, which generates dioxetane intermediates by a mechanism similar to that of peroxynitrite (24). This produced similar levels of chemiluminescence (Fig. 4A, fig. S4B).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] source
- Findingown data
Oxidation of 5-hydroxyindole-2-carboxylic acid, which lacks an OH group on DHICA's 6-membered ring, still produced chemiluminescence and CPD.
“When we blocked the reactivity of DHICA's 6-membered ring by omitting an OH group (5-hydroxyindole-2-carboxylic acid) (fig. S6A), oxidation still produced chemiluminescence (fig. S6B,C) and CPD (fig. S6D), suggesting that 2 is the predominant product.”
Quote in the paperSubstantial claim - Findingown data
DBAS reduced CPD production by 50-90% in the cell-free oxidation reactions.
“However we found that DBAS, which redirects triplet energy toward luminescence, reduced CPD production by 50-90% (Fig. 4C, fig. S4C).”
Quote in the paperSubstantial claim - Interpretationreasoning
Because most epidermal cells were keratinocytes that receive pigment from melanocytes, melanin content rather than melanin synthesis is likely the crucial requirement for dark CPD induction.
“Most epidermal cells were keratinocytes, which receive pigment from the melanocytes, suggesting that melanin content rather than synthesis was the crucial requirement for dark CPD induction.”
Quote in the paperSubstantial claim - Interpretationreasoning
The UVA-induced nitrotyrosine increase represents a roughly 400-fold spike in peroxynitrite flux per hour.
“This represents a ~400 fold spike in the flux of peroxynitrite per hour.”
Quote in the paperNot a substantial claim - Interpretationown data
Pigmented melanocytes produce dark CPD after UV exposure has ended.
“We conclude that pigmented melanocytes induce “dark CPD” after UV exposure ends.”
Quote in the paperSubstantial claim - Interpretationown data
UV-induced superoxide and nitric oxide lead to a high-energy triplet state moiety that creates dark CPD by energy transfer.
“These results provide direct evidence that UV-induced superoxide and nitric oxide lead to a high-energy triplet state moiety, which then creates a dark CPD by energy transfer.”
Quote in the paperSubstantial claim - Interpretationown data
The data suggest that chemiexcitation may be important in skin.
“Our data suggest that this may be the case in skin.”
Quote in the paperSubstantial claim - Interpretationown data
Structure 2 is the predominant DHICA oxidation product.
“suggesting that 2 is the predominant product.”
Quote in the paperSubstantial claim - Interpretationown data
Half or more of the CPD in a melanocyte arise after UV exposure ends.
“The consequence is that half or more of the CPD in a melanocyte arise after UV exposure ends.”
Quote in the paperSubstantial claim - Premisecitation
Melanin synthesis generates reactive oxygen species, especially during pheomelanin synthesis.
“Melanin synthesis itself generates ROS, especially synthesis of pheomelanin (7).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [7] source
- Interpretationreasoning
In vivo, the same appears true of keratinocytes, which receive melanosomes donated by melanocytes.
“In vivo the same appears to be true of keratinocytes, which receive melanosomes donated by melanocytes.”
Quote in the paperNot a substantial claim - Interpretationown data
Based on mass spectrometry with albino murine melanocytes, the no-UV CPD level corresponds to about 1 CPD per 24 kb of DNA created solely by oxidized melanin.
“Based on our mass spectrometry data with albino murine melanocytes (Fig. 2), this value is approximately 1 CPD per 24 kb of DNA created solely by oxidized melanin.”
Quote in the paperSubstantial claim - Premisecitation
Reactive oxygen species can be produced in cells for long periods after UVA exposure.
“Because ROS can be produced in cells for long periods after UVA exposure (19), we tested the ROS scavengers N-acetylcysteine and α-tocopherol (vitamin E).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19] source
- Interpretationown data
Melanin and melanin fragments can act as molecular vectors that acquire an electronically excited triplet state, probably at a carbonyl arising from a dioxetane intermediate.
“Together, these results indicate that melanin and melanin fragments are capable of acting as the molecular vectors that acquire an electronically excited triplet state, probably at a carbonyl arising from a dioxetane intermediate.”
Quote in the paperSubstantial claim - Premisecitation
UVA generates primarily TT CPD, with TC and CT CPD together making up only 10-30% of these three CPD types.
“UVA generates primarily TT CPD, with TC and CT CPD together contributing only 10-30% of these three CPD types (13).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] source
- Interpretationreasoning
If the same holds for human skin, past measurements of CPD immediately after UV exposure have underestimated the consequences of UV exposure.
“If the same holds for human skin, this would mean that past measurements of CPD immediately after UV exposure have underestimated the consequences of UV exposure.”
Quote in the paperNot a substantial claim - Interpretationown data
In cells exposed to UV, melanin or its constituents can enter the nucleus.
“We conclude that, in cells exposed to UV, melanin or its constituents are able to enter the nucleus.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The dark cytoplasmic granules seen in unirradiated normal melanocytes are melanin aggregates located in melanosomes, coated vesicles, and endoplasmic reticulum.
- May combine two claims. 33
- Classified as probably not a substantial claim. 11
May combine two claims.
Interpretationown dataThe UVB dark CPD process depends on melanin and is distinct from delayed CPD reported in other cell types after UVC or UVB.
“The UVB process was also dependent on melanin and thus it differs from the delayed production of CPD that has been reported occasionally in other cell types after UVC or UVB exposure (16-18).”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [16]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [17] source
- cites [18] source
The UVA irradiation and NADPH oxidase sections describe reactive oxygen species in UVA-exposed keratinocytes, not UVB-induced dark CPDs. Searches for melanin, CPDs, and delayed CPD production after UVB or UVC found no passage addressing the claim in our copy. (LLM, conf=0.75)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationUVA induces melanoma in mice and in humans who use tanning beds, but it is inefficient at making the cytosine-containing CPD that cause C→T mutations.
“The lower-energy UVA (315-400 nm), which constitutes ~95% of the ultraviolet energy that penetrates the atmosphere, also induces melanoma in mice and in humans who use tanning beds, but it is inefficient at making the cytosine-containing CPD that cause C→T mutations (12, 13).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [12] source
The Abstract Results report elevated melanoma odds among indoor tanners, including users of primarily UVA-emitting devices. The Discussion cautions that the study cannot determine whether UVA or UVB caused those associations. The paper does not report melanoma induction in mice or address cytosine-containing CPDs and C→T mutations. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [13] source
- Rests on an assumption: UVA accounts for about 95% of the ultraviolet energy that reaches the Earth's surface.
May combine two claims.
PremisecitationUV-irradiated melanin, especially pheomelanin, triggers apoptosis, reactive oxygen species production, and DNA strand breaks.
“UV-irradiated melanin, especially pheomelanin, triggers apoptosis and production of reactive oxygen species (ROS) and DNA strand breaks (5, 6).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [5] source
- cites [6] source
The Abstract concludes that UV-irradiated melanin, particularly pheomelanin, photosensitizes nearby cells to apoptosis. It also says irradiated melanin generates reactive oxygen species in vitro or in cultured cells, which can indirectly cause DNA strand breaks. The claim overstates the strand-break finding: the Results report no detectable signal above background for single-strand breaks immediately after UV irradiation of mouse skin. (LLM, conf=0.88)
Experimental — accuracy not yet measured
May combine two claims.
Findingown dataUVA-irradiated melanocytes generated ultra-weak chemiluminescence for several hours after irradiation, and only melanin-containing cells did so.
“UVA-irradiated melanocytes generated ultra-weak chemiluminescence for several hours post-irradiation and only in cells containing melanin (Fig. 3F,G).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataBasal 3-nitrotyrosine nitration activity is present without UV, is located primarily in the nucleus, and requires melanin.
“Assays for 3-nitrotyrosine revealed that basal nitration activity was present even without UV, that it was located primarily in the nucleus, and that its appearance required melanin (Fig. 3D,E) (fig. S2D).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataHuman melanocytes also generate dark CPD after UVA or UVB exposure, with inter-individual variation especially for UVA.
“Human melanocytes also generated dark CPD after UVA or UVB exposure (Fig. 1E, fig. S1I) although there was inter-individual variation in the response, particularly for UVA.”
Quote in the paperSubstantial claimMay combine two claims.
FindingreasoningDBAS, which diverts triplet energy to luminescence, also blocked dark CPD.
“Because DBAS diverts triplet energy to luminescence, this compound also blocked dark CPD (fig. S2E).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataN-acetylcysteine suppressed dark CPD production by 64%, and α-tocopherol abolished it.
“The former suppressed production of dark CPD by 64% and the latter abolished it (figs. S2A,B).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataUnirradiated normal melanocytes, but not albino melanocytes, showed dark granules in the cytoplasm, especially near the nucleus.
“Unirradiated normal melanocytes but not albino melanocytes showed dark granules in the cytoplasm, especially in the perinuclear area (fig. S5).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe eumelanin monomer DHICA and the pheomelanin monomer 5SCD generated chemiluminescence when oxidized.
“The eumelanin monomer 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and the pheomelanin monomer 5-S-cysteinyldopa (5SCD) also generated chemiluminescence when oxidized (Fig. 4A).”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Findingown dataScanning the HPLC fraction across the small-molecule region revealed four principal m/z peaks, with the second largest at 224 daltons.
“Scanning this fraction of the HPLC eluate across the small-molecule region of the mass spectrometer revealed four principal m/z peaks, of which the second largest was 224 daltons (Fig. 4F).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe chemiluminescence began immediately and continued for more than 10 minutes.
“We found that chemiluminescence began immediately and proceeded for >10 min.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataDark CPD were also induced during UVA irradiation itself, because CPD were inhibited below the 0 h level.
“CPD were inhibited to a level below that at 0 h, indicating that dark CPD were also induced during the irradiation itself.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe absence of delayed CPD in albino melanocytes implicates melanin and excludes photosensitizing compounds in the growth medium as the cause.
“The negative result with albino melanocytes implicated melanin in the process and ruled out the involvement of photosensitizing compounds in the growth medium.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataPheomelanin is both a weaker shield against normal CPD formation and a stronger generator of dark CPD.
“This suggests that pheomelanin is both a poorer shield against normal CPD formation and a more potent dark CPD generator.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductown dataMass spectrometry ruled out cross-reaction of the ELISA and comet assays with melanin-DNA adducts and ruled out greater antibody or endonuclease access due to DNA conformation change after UV.
“Mass spectrometry ruled out the possibilities that (i) the ELISA and comet assays cross-reacted with melanin-DNA adducts and (ii) the delayed CPD appearance reflected greater access of the antibody or endonuclease due to a change in DNA conformation after UV exposure.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenThe inter-individual variation in human melanocyte dark CPD likely reflects genetic differences between donors.
“This likely reflects genetic differences between the donors.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationBecause triplet carbonyls last about 10 μs, a chemiluminescence signal lasting hours indicates ongoing creation of triplet states.
“The lifetime of triplet carbonyls is ~10 μs (24), so a signal persistent over the course of hours indicates ongoing creation.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] source
May combine two claims.
PremisecitationBlondes and redheads have a higher pheomelanin-to-eumelanin ratio and a 2-4 times greater melanoma risk than dark-haired individuals, and the ratio accounts for some of this risk.
“Blondes and redheads, who have a higher ratio of yellow pheomelanin to brown eumelanin in their skin and hair, have a 2-4 times greater risk for melanoma than dark-haired individuals and the pheomelanin/eumelanin ratio accounts for some of this risk (2).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] source
May combine two claims.
PremisecitationUV-signature mutations arise from CPD, which join adjacent pyrimidines and distort the DNA helix.
“Such mutations arise from cyclobutane pyrimidine dimers (CPD), which join adjacent pyrimidines to distort the DNA helix (10, 11);”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAn effect of antioxidants on CPD detectable immediately after UV has been reported, but it was linked to changes in chromatin structure.
“An effect of antioxidants on CPD detectable immediately after UV has been reported, but was linked to changes in chromatin structure (20).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] source
Classified as probably not a substantial claim.
PremisecitationA diagnostic for excited triplet states is that their energy can discharge as ultra-weak blue or green luminescence.
“A diagnostic for excited triplet states is that their energy can also discharge via ultra-weak blue or green luminescence (23).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] source
May combine two claims.
PremisecitationThe DHICA analog of the predicted eumelanin degradation product has a molecular weight of 225 daltons and would be highly polar.
“The DHICA analog of the predicted eumelanin degradation product (29) (Fig. 4E, structure 1) has a molecular weight of 225 daltons and would be highly polar.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] source
May combine two claims.
InterpretationreasoningThe sustained time course of dark CPD generation can be explained by prolonged UV induction of NOX and iNOS, peroxynitrite-induced melanin solubilization or release of pre-melanin monomers, and migration to the nucleus.
“The sustained time course of dark CPD generation can be accounted for by the prolonged steps of UV-induction of NOX and iNOS, peroxynitrite-induced solubilization of melanin to fragments or release of pre-melanin monomers from UV-damaged melanosomes and vesicles, and migration to the nucleus.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningMelanin may be carcinogenic as well as protective against cancer.
“A consequence of these events is that melanin may be carcinogenic as well as protective against cancer.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationAn alternative reaction forms a dioxetane moiety at the pyrrole ring, also leading to a polar structure of 225 daltons.
“An alternative reaction is formation of a dioxetane moiety at the pyrrole ring (32), also leading to a polar structure of 225 daltons (structure 2).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [32] source
Probably not a substantial claim: may not pass S2 (checkable).
PremisecitationMelanin is an unusual polymer whose properties set the stage for the described events.
“Melanin is an unusual polymer whose properties set the stage for the events we have described (33).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [33] source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIt was proposed long ago that chemiexcitation has broad importance in biology.
“It was proposed long ago that chemiexcitation – the creation of chemical reaction products containing excited electrons that underlie bioluminescence in lower organisms – has broad importance in biology (22, 23).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationUV exposure excites melanin rings to an energy that, especially for pheomelanin, ejects an electron captured by oxygen to yield more superoxide.
“UV exposure additionally excites the rings to an energy that, especially for pheomelanin, ejects an electron that is captured by oxygen to yield more O2•- (5, 34).”
Quote in the paperSubstantial claim0 of 2 sources checkedClassified as probably not a substantial claim. May combine two claims.
PremisecitationMelanin monomer synthesis is a redox reaction that releases superoxide, and melanosomes are assembled in the perinuclear space.
“Peroxynitrite's presence in the nucleus without UV exposure is plausible because synthesis of melanin monomers is a redox reaction that releases O2•– (7) and melanosomes are assembled in the perinuclear space.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] source
May combine two claims.
PremisecitationMelanin monomers are lipophilic and potentially able to enter the nucleus, and they are concentrated in perinuclear coated vesicles before transfer to melanosomes.
“These monomers are lipophilic and are therefore potentially able to enter the nucleus, and are concentrated in perinuclear coated vesicles before transfer to melanosomes (27).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [27]
May combine two claims.
InterpretationreasoningThese excited products transfer triplet energy to DNA hours after UV exposure, creating mutagenic CPD in the dark.
“These evanescent electronically excited products transfer their triplet energy to DNA hours after the original UV exposure, creating mutagenic cyclobutane pyrimidine dimers in the dark.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataExposing melanin-containing cells to UV induces superoxide and nitric oxide, causes an orders-of-magnitude peroxynitrite spike that degrades melanin, allows melanin-like granules in the nucleus, and excites melanin derivatives to a triplet state with the energy of a UV photon.
“In summary, we have shown that exposing melanin-containing cells to UV radiation induces superoxide and nitric oxide, causing an orders-of-magnitude peroxynitrite spike that degrades melanin, allows melanin-like granules to appear in the nucleus, and excites melanin derivatives to a triplet state that has the high energy of a UV photon (Fig. 5).”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationNADPH oxidase is a longer-lasting source of superoxide in cells and is rapidly induced by UVA.
“A longer-lasting source of O2•– in cells is NADPH oxidase (NOX), which is rapidly induced by UVA (19).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19] source
Classified as probably not a substantial claim.
PremisecitationPeroxynitrite is generated by the reaction of superoxide with nitric oxide.
“One of the few biologically-synthesized molecules that can initiate such “photochemistry in the dark” (22, 23) is peroxynitrite (ONOO–) (24), which is generated by the reaction of O2•– with nitric oxide (NO•).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] source
Classified as probably not a substantial claim.
InterpretationreasoningThe slow course of dark photochemistry allows intervention.
“One benefit of dark photochemistry's slow course is that it allows intervention.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationMelanin protects against sunlight-induced burns, DNA damage, and skin cancer because of its broad absorption spectrum and possibly radical scavenging.
“The pigment melanin protects against sunlight-induced burns, DNA damage, and skin cancer due to an unusually broad absorption spectrum and perhaps radical scavenging activity (1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] source
May combine two claims.
PremisecitationNOX and iNOS are UV-inducible within minutes and are expressed in melanocytes, including nuclear NOX4.
“NOX and the NO• generator iNOS are UV-inducible within minutes and are expressed in melanocytes, including nuclear NOX4 (25).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] source
May combine two claims.
Premisecitationα-Tocopherol is an antioxidant and also inactivates dioxetanes by converting them to a pair of diols.
“A blocker of dark CPD, α-tocopherol (vitamin E), is not only an antioxidant but also inactivates dioxetanes by converting them to a pair of diols (35).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] source
Classified as probably not a substantial claim. May combine two claims.
PremisecitationMelanin polymer rapidly solubilizes when exposed to hydrogen peroxide, and its degradation by peroxidation or UV-photoionization has been proposed to involve dioxetane and triplet carbonyls.
“Melanin polymer rapidly solubilizes when exposed to hydrogen peroxide (H2O2) (28) and its degradation by peroxidation or UV-photoionization has been proposed to involve dioxetane and triplet carbonyls (29, 30).”
Quote in the paperSubstantial claim0 of 3 sources checked
The paper relies on this without support.
UVA accounts for about 95% of the ultraviolet energy that reaches the Earth's surface.
“The lower-energy UVA (315-400 nm), which constitutes ~95% of the ultraviolet energy that penetrates the atmosphere, also induces melanoma in mice and in humans who use tanning beds, but it is inefficient at making the cytosine-containing CPD that cause C→T mutations (12, 13).”
The paper relies on this without support.
Disorders of CPD repair, such as xeroderma pigmentosum, increase childhood melanoma risk by 10,000-fold.
“genetic disorders of CPD repair such as xeroderma pigmentosum elevate the risk for childhood melanoma by 10,000-fold.”
The paper relies on this without support.
Peroxynitrite and nitric oxide can diffuse far enough from where they are made to reach their target molecules.
“Peroxynitrite and NO• are stable enough to diffuse significant distances from the site of generation to the target molecule.”
The authors state this as an assumption.
The dark cytoplasmic granules seen in unirradiated normal melanocytes are melanin aggregates located in melanosomes, coated vesicles, and endoplasmic reticulum.
“We presume these are melanin aggregates in melanosomes, coated vesicles, and endoplasmic reticulum because they have the same size and cellular locations as granules seen in melanocytes immunostained for tyrosinase (31).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
This result suggests melanin-like reactants might create dCPDs by a reaction other than the indole ring dioxetane proposed earlier.
“This result suggests that melanin-like reactants might be creating dCPDs by a reaction other than the indole ring dioxetane proposed in reference (32).”
From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [32]
In “Electronically Excited Melanin as a Molecular Vector” (page unavailable), the paper describes a pyrrole-ring dioxetane as an alternative reaction and reports evidence suggesting it is the predominant product. It does not propose the indole-ring dioxetane mechanism that the citing sentence attributes to it. (LLM, conf=0.83)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredUV-filtering melanin is present in all keratinocytes of the epidermis but absent in corneal epidermal cells.
“This means that UV-filtering melanin can be found in all keratinocytes of the epidermis whereas it is absent in corneal epidermal cells [ 70 ].”
From Faster DNA Repair of Ultraviolet-Induced Cyclobutane Pyrimidine Dimers and Lower Sensitivity to Apoptosis in Human Corneal Epithelial Cells than in Epidermal Keratinocytes (2016) · cites this paper as [70]
The section on delayed cyclobutane pyrimidine dimer induction says epidermal keratinocytes receive pigment from melanocytes, and the paper describes melanin as shielding against UV damage. It does not establish that all epidermal keratinocytes contain melanin or that corneal epidermal cells lack it. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe generation of ROS and peroxynitrites, mainly in mouse melanocytes that only synthesize pheomelanin, contributes to delayed induction of cyclobutane pyrimidine dimers post-UV exposure, increasing the risk for UV signature mutations prevalent in melanoma.
“The generation of ROS and peroxynitrites, mainly in mouse melanocytes that only synthesize pheomelanin, contributes to the delayed induction of cyclobutane pyrimidine dimers, the major form of DNA photoproducts, post-UV exposure, which increases the risk for UV signature mutations that are prevalent in melanoma [ 20 ].”
From Differential Induction of Reactive Oxygen Species and Expression of Antioxidant Enzymes in Human Melanocytes Correlate with Melanin Content: Implications on the Response to Solar UV and Melanoma Susceptibility (2022) · cites this paper as [20]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn the first step of that reaction, brief UV exposure activates NOS and NOX to generate nitric oxide and superoxide for hours afterward; the induction mechanism is unknown.
“a brief UV exposure activates the enzymes nitric oxide synthase (NOS) and NADPH oxidase (NOX) to generate the radicals nitric oxide (•NO) and superoxide (O2•−) for hours afterward; the mechanism of induction is still not known.”
From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [32]
The Photochemical Pathway section says NOX and iNOS are UV-inducible within minutes and identifies them as sources of superoxide and nitric oxide; the Proposed Scheme describes prolonged UV induction of both enzymes. The paper does not establish that both radicals are generated for hours after exposure. It says the specific isozymes remain unidentified, but does not explicitly say that the mechanism of enzyme induction is unknown. Page numbers are unavailable in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe melanin-to-DNA chemiexcitation process is initiated by nitric oxide and superoxide, radicals triggered by ultraviolet light or inflammation.
“That process was initiated by nitric oxide and superoxide, radicals triggered by ultraviolet light or inflammation.”
From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [32]
The “Proposed Scheme for the Participation of Melanin in Melanoma Development” section says UV exposure induces superoxide and nitric oxide, which lead to excitation of melanin derivatives and subsequent DNA photoproducts. The “Photochemical Pathway” section likewise describes their role in producing peroxynitrite. Our copy does not attribute initiation of this process to inflammation. (LLM, conf=0.88)
Experimental — accuracy not yet measured
In the second step, melanin or its precursor monomer is oxidized to a radical; based on analogous reactions, ambient O2 is proposed to add and form a peroxyl radical that cyclizes into a dioxetane.
“Based on analogous reactions in the literature, it is proposed that ambient O2 adds to create a peroxyl radical, which then cyclizes to create a strained 4-atom ring containing C–O–O–C, termed a dioxetane”
From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [32]
The Photochemical Pathway section describes dioxetane as a strained four-membered ring peroxide, and the Proposed Scheme section speculates that a peroxynitrite–melanin reaction produces a dioxetane intermediate (page numbers unavailable). Neither passage proposes the specific sequence in which ambient O₂ adds to form a peroxyl radical that then cyclizes. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn mammals, chemiexcitation was discovered as direct energy transfer from excited melanin to DNA, producing the lethal and carcinogenic cyclobutane pyrimidine dimer.
“In mammals, chemiexcitation was discovered as energy transferred directly from excited melanin to DNA, creating the lethal and carcinogenic cyclobutane pyrimidine dimer.”
From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [32]
The Proposed Scheme section (page unavailable) says excited melanin derivatives transfer energy to DNA after UV exposure, creating mutagenic cyclobutane pyrimidine dimers. The Abstract links these dimers to melanoma mutations, but the copy does not describe them as lethal; it also identifies melanin fragments or derivatives, rather than intact melanin, as the excited products. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe chemiexcitation events were discovered in melanocyte cell cultures and murine skin using a fluorescent triplet-state reporter, blocking with vitamin E or sorbate, and identifying dCPDs by mass spectrometry and immunohistochemistry.
“The chemiexcitation events were discovered in melanocyte cell cultures and in murine skin, using a fluorescent triplet-state reporter to detect the transient triplet state, blocking these events with the radical scavenger vitamin E or the triplet-specific quencher sorbate, and identifying dCPDs using mass spectrometry and immunohistochemistry.”
From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [32]
The Delayed Cyclobutane Pyrimidine Dimer Induction section reports dark CPDs in cultured melanocytes and mouse epidermis, while the Photochemical Pathway section describes a luminescent triplet-energy reporter and says vitamin E abolished dark-CPD production. The Cytosine-containing Dark CPD section confirms identification by mass spectrometry. The available passages describe immunofluorescence rather than immunohistochemistry and do not establish that sorbate blocked the events; the Electronically Excited Melanin section says sorbate could not be tested in its cell-free reaction. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThe authors' laboratory discovered that chemiexciting melanin sends melanocytes toward melanoma even in the dark.
“Recently our laboratory discovered that chemiexciting the skin pigment melanin sends melanocytes down the path to melanoma even in the dark”
From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [32]
The pyrrole ring was implicated as a site of dioxetane formation, and the catechol ring of eumelanin has also been proposed as a site for dioxetane formation.
“The pyrrole ring was implicated as the site of a dioxetane (Fig. 4c) (32); the catechol ring of eumelanin has also been proposed as a site for dioxetane formation (43).”
From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [32]
Pheomelanins have been implicated in UV-radiation-independent carcinogenic contributions to melanomagenesis by inducing oxidative DNA damage.
“Pheomelanins have also been implicated in UV-radiation-independent carcinogenic contributions to melanomagenesis by inducing oxidative DNA damage [65,66,67].”
From “Fifty Shades” of Black and Red or How Carboxyl Groups Fine Tune Eumelanin and Pheomelanin Properties (2016) · cites this paper as [67]
MAA may have even greater potential for photoprotection over current filters.
“This shows that MAA may have even greater potential for photoprotection over current filters”
From Mycosporine-Like Amino Acids for Skin Photoprotection (2019) · cites this paper as [5]
Delayed (dark) CPD formation suggests that CPD can form for hours after exposure through a triplet photoexcitation mechanism.
“the recent discovery of delayed (also know as ‘dark’) CPD formation, which suggests that CPD can form for hours after exposure through a triplet photoexcitation mechanism [5]”
From Mycosporine-Like Amino Acids for Skin Photoprotection (2019) · cites this paper as [5]
The consequences of UVA exposure for the development of melanoma have been underestimated.
“Therefore, this work is a strong indication that the consequences of UVA exposure for the development of melanoma have been underestimated.”
From Sunlight damage to cellular DNA: focus on oxidatively generated lesions (2017) · cites this paper as [99]
CPDs can continue to be generated in the skin for more than 3 hours after exposure to UVA.
“Recently, it was demonstrated that CPDs could also continue to be generated in the skin for more than 3 h after exposure to UVA [99].”
From Sunlight damage to cellular DNA: focus on oxidatively generated lesions (2017) · cites this paper as [99]
UVB irradiation can cause loss of cellular integrity, direct damage to DNA and trigger various cellular responses including apoptosis and inflammation in skin cells including melanocytes.
“UVB irradiation can cause the loss of cellular integrity, direct damage to DNA and trigger various cellular responses including apoptosis [3] and inflammation [4] in skin cells including melanocytes (MC).”
From Nrf2 in keratinocytes modulates UVB-induced DNA damage and apoptosis in melanocytes through MAPK signaling (2017) · cites this paper as [3]
ROS and RNS generated in melanocytes after UVA radiation lead to production of dark CPDs hours after UVA exposure.
“ROS and reactive nitrogen species (RNS) generated in melanocytes in response to UVA radiation lead to the production of “dark CPDs” hours after UVA exposure74.”
From Mechanisms and prevention of <scp>UV</scp>‐induced melanoma (2018) · cites this paper as [74]
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Self-citation
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Del Bino, S., Duval, C., & Bernerd, F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092668 · Cited by 315 · see citing works
Melanoma, Melanin, and Melanogenesis: The Yin and Yang Relationship
Slominski, R. M., Sarna, T., Plonka, P. M., Raman, C., Brożyna, A. A., & Slominski, A. T. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.842496 · Cited by 298 · see citing works
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Palmitoylation-dependent activation of MC1R prevents melanomagenesis
Chen, S., Zhu, B., Yin, C., Liu, W., Han, C., Chen, B., Liu, T., Li, X., Chen, X., Li, C., et al. (2017) · Nature · doi:10.1038/nature23887 · Cited by 236 · see citing works
“Activation of MC1R in melanocytes by α -melanocyte-stimulating hormone ( α -MSH) 9 stimulates cAMP signaling and melanin production and enhances DNA repair after UV irradiation (UVR) 10–16 .”
Role of reactive oxygen species in ultraviolet-induced photodamage of the skin
Wei, M., He, X., Liu, N., & Deng, H. (2024) · Cell Division · doi:10.1186/s13008-024-00107-z · Cited by 244 · see citing works
Visible light. Part I: Properties and cutaneous effects of visible light
Austin, E., Geisler, A. N., Nguyen, J. K., Kohli, I., Hamzavi, I. H., Lim, H. W., & Jagdeo, J. R. (2021) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2021.02.048 · Cited by 247 · see citing works
Mechanisms of UV-induced mutations and skin cancer
Pfeifer, G. P. (2020) · Genome Instability & Disease · doi:10.1007/s42764-020-00009-8 · Cited by 237 · see citing works
Blue light-induced oxidative stress in live skin
Nakashima, Y., Ohta, S., & Wolf, A. M. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.03.010 · Cited by 222 · see citing works
Photosensitization Reactions of Biomolecules: Definition, Targets and Mechanisms
Baptista, M. S., Cadet, J., Greer, A., & Thomas, A. H. (2021) · Photochemistry and Photobiology · doi:10.1111/php.13470 · Cited by 205 · see citing works
Baker, L. A., Marchetti, B., Karsili, T. N. V., Stavros, V. G., & Ashfold, M. N. R. (2017) · Chemical Society Reviews · doi:10.1039/c7cs00102a · Cited by 200 · see citing works
Bernerd, F., Passeron, T., Castiel, I., & Marionnet, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158243 · Cited by 179 · see citing works
“Noticeably, the CPDs generated through this indirect process have been shown to occur after rather than during UV exposure and are thus referred to as “dark CPDs” [49].”
BackgroundInfluentialLi, Z., Chen, Z.-D., Chen, H., Chen, K.-B., Tao, W., Ouyang, X.-K., Mei, L., & Zeng, X.-W. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.01.038 · Cited by 170 · see citing works
“energy into heat, so it can protect organisms from ultraviolet damage [130,131].”
BackgroundMITF and UV responses in skin: From pigmentation to addiction
Nguyen, N. T., & Fisher, D. E. (2018) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12726 · Cited by 161 · see citing works
“However, the Brash group discovered that after UVA or UVB exposure, melanin- containing murine melanocytes continued to generate CPDs for at least 3 hr, while CPD induction lasted only picoseconds in fibroblasts and albino melanocytes (Premi et al., 2015).”
BackgroundMimicking Melanosomes: Polydopamine Nanoparticles as Artificial Microparasols
Huang, Y., Li, Y., Hu, Z., Yue, X., Proetto, M. T., Jones, Y., & Gianneschi, N. C. (2017) · ACS Central Science · doi:10.1021/acscentsci.6b00230 · Cited by 163 · see citing works
“7,49,50 Therefore, we tested for protective qualities of MelNPs by analyzing DNA damage in HEKa cells after treatment with MelNPs followed by UV irradiation (Figure 5).”
Protein oxidation, UVA and human DNA repair
Karran, P., & Brem, R. (2016) · DNA repair · doi:10.1016/j.dnarep.2016.05.024 · Cited by 163 · see citing works
Mycosporine-Like Amino Acids for Skin Photoprotection
Lawrence, K. P., Long, P. F., & Young, A. R. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867324666170529124237 · Cited by 157 · see citing works
Roles of UVA radiation and DNA damage responses in melanoma pathogenesis
Khan, A. Q., Travers, J. B., & Kemp, M. G. (2018) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22176 · Cited by 152 · see citing works
“However, UVA has also long been recognized for its indirect effects on DNA damage formation through the excitation of vari- ous cellular photosensitizers, such as flavin, melanin, riboflavin, and porphyrins [Wondrak et al., 2006; Premi et al., 2015].”
BackgroundInfluentialRadice, M., Manfredini, S., Ziosi, P., Dissette, V., Buso, P., Fallacara, A., & Vertuani, S. (2016) · Fitoterapia · doi:10.1016/j.fitote.2016.09.003 · Cited by 149 · see citing works
Lawrence, K. P., Douki, T., Sarkany, R. P. E., Acker, S., Herzog, B., & Young, A. R. (2018) · Scientific Reports · doi:10.1038/s41598-018-30738-6 · Cited by 143 · see citing works
Self-citationCordero, R. J. B., & Casadevall, A. (2020) · Current Biology · doi:10.1016/j.cub.2019.12.042 · Cited by 141 · see citing works
Photodegradation of Eumelanin and Pheomelanin and Its Pathophysiological Implications
Ito, S., Wakamatsu, K., & Sarna, T. (2018) · Photochemistry and Photobiology · doi:10.1111/php.12837 · Cited by 136 · see citing works
“in melanocytes for >3 h after exposure to UVA (“dark CPDs”), involving UV-induced reactive oxygen and nitrogen species and melanin pigment (13).”
BackgroundSelf-citationMicillo, R., Panzella, L., Koike, K., Monfrecola, G., Napolitano, A., & D’Ischia, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17050746 · Cited by 135 · see citing works
The metabolism of melanin synthesis—From melanocytes to melanoma
Snyman, M., Walsdorf, R. E., Wix, S., & Gill, J. G. (2024) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.13165 · Cited by 151 · see citing works
““Dark” CPDs are formed in melanin-containing keratinocytes and melanocytes > 3 h after UVA or B exposure due to the resulting ROS, and were most prominent in pheomelanin containing cells (Premi et al., 2015).”
BackgroundMycosporine-Like Amino Acids: Making the Foundation for Organic Personalised Sunscreens
Rosic, N. N. (2019) · Marine Drugs · doi:10.3390/md17110638 · Cited by 133 · see citing works
Oxidatively-generated damage to DNA and proteins mediated by photosensitized UVA
Brem, R., Guven, M., & Karran, P. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.10.488 · Cited by 136 · see citing works
“Endogenous UVA chromophores have not been fully characterized, although porphyrins, flavins [3], melanin [4] and UVB photoproducts of tryptophan (6-formylindolo[3,2-b]carbazole, FICZ) [5] are among the potential candidates.”
BackgroundThe impact of skin colour on human photobiological responses
Fajuyigbe, D., & Young, A. R. (2016) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12511 · Cited by 108 · see citing works
Vieyra-Garcia, P. A., & Wolf, P. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107784 · Cited by 114 · see citing works
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Deciphering UV‐induced DNA Damage Responses to Prevent and Treat Skin Cancer
Lee, J. W., Ratnakumar, K., Hung, K., Rokunohe, D., & Kawasumi, M. (2020) · Photochemistry and Photobiology · doi:10.1111/php.13245 · Cited by 112 · see citing works
Photolyase-Like Catalytic Behavior of CeO2
Tian, Z., Yao, T., Qu, C., Zhang, S. M., Li, X., & Qu, Y. (2019) · Nano Letters · doi:10.1021/acs.nanolett.9b03836 · Cited by 102 · see citing works
de la Coba, F., Aguilera, J. M., Korbee, N., de Gálvez, M. V., Herrera‐Ceballos, E., Álvarez‐Gómez, F., & Figueroa, F. L. (2019) · Marine Drugs · doi:10.3390/md17010055 · Cited by 108 · see citing works
“The so-called dark CPDs are mediated by ROS and the use of systemic or topical antioxidants could prevent their synthesis [85].”
BackgroundNguyen, A. K., Goering, P. L., Elespuru, R. K., et al. (2020) · Polymers · doi:10.3390/polym12071489 · Cited by 103 · see citing works
“Given the literature demonstrating and proposing mechanisms of free-radical mediated mutagenicity, it is surprising that almost no studies have investigated the mutagenicity of the GelMA + LAP photopolymer, or of photoinitiators in general, despite the large number of studies evaluating this specific combination [14,1…”
BackgroundMC1R: Front and Center in the Bright Side of Dark Eumelanin and DNA Repair
Swope, V. B., & ABDEL‐MALEK, Z. A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092667 · Cited by 105 · see citing works
“An intriguing observation was the continuous generation of CPD in mouse skin irradiated with ultraviolet A (UVA) for hours after the cessation of irradiation [37].”
BackgroundUltraviolet Radiation Biological and Medical Implications
Al-Sadek, T., & Yusuf, N. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46030126 · Cited by 104 · see citing works
“These dioxetanes then break down into two carbonyls, one of which is an excited-state triplet carbonyl with energy equivalent to a UV photon [18].”
BackgroundGenomic sites hypersensitive to ultraviolet radiation
Premi, S., Han, L., Mehta, S., Knight, J., Zhao, D., Palmatier, M. A., Kornacker, K., & Brash, D. E. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1907860116 · Cited by 95 · see citing works
Self-citationBio-Applications of Multifunctional Melanin Nanoparticles: From Nanomedicine to Nanocosmetics
Mavridi‐Printezi, A., Guernelli, M., Menichetti, A., & Montalti, M. (2020) · Nanomaterials · doi:10.3390/nano10112276 · Cited by 100 · see citing works
“The experimental results demonstrated that pheomelanin not only was poorly effective in protecting from CPD formation but it also induced dark CPD generation [53].”
BackgroundNahhas, A. F., ABDEL‐MALEK, Z. A., Kohli, I., Braunberger, T. L., Lim, H. W., & Hamzavi, I. H. (2018) · Photodermatology Photoimmunology & Photomedicine · doi:10.1111/phpp.12423 · Cited by 96 · see citing works
Delinasios, G. J., Karbaschi, M., Cooke, M. S., & Young, A. R. (2018) · Scientific Reports · doi:10.1038/s41598-017-18924-4 · Cited by 95 · see citing works
“13 for “dark” CPD. Whilst it is not possible to distinguish between ‘dark” CPD and the formation of those from direct UVR absorption (“light” CPD), we speculate that CPD burden at time 0 h primarily represents the latter and that the peak at 0.5–1 h represents the addition of “dark” to “light” CPD.”
BackgroundResultInfluentialCurrent challenges in photoprotection.
Lim, H., Arellano-Mendoza, M., & Stengel, F. (2017) · Journal of American Academy of Dermatology · doi:10.1016/j.jaad.2016.09.040 · Cited by 85 · see citing works
UV and ionizing radiations induced DNA damage, differences and similarities
Ravanat, J.-L., & Douki, T. (2016) · Radiation Physics and Chemistry · doi:10.1016/j.radphyschem.2016.07.007 · Cited by 94 · see citing works
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Targeting MC1R depalmitoylation to prevent melanomagenesis in redheads
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Autophagy in UV Damage Response
Sample, A., & He, Y. (2016) · Photochemistry and Photobiology · doi:10.1111/php.12691 · Cited by 90 · see citing works
“The abundance of UVA-induced CPDs, and ineffective repair of these lesions, may therefore form a significant source of UVA-induced skin damage (56).”
BackgroundUV Radiation in DNA Damage and Repair Involving DNA-Photolyases and Cryptochromes
Vechtomova, Y. L., Telegina, T. A., Buglak, A. A., & Kritsky, M. (2021) · Biomedicines · doi:10.3390/biomedicines9111564 · Cited by 92 · see citing works
“However, as previously described, melanin can also be carcinogenic, contributing to the formation of CPD even after irradiation termination [8,26].”
BackgroundZheng, X., Jia, Y., & Chen, A. (2021) · Nature Communications · doi:10.1038/s41467-021-25178-2 · Cited by 90 · see citing works
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Melanin Transfer and Fate within Keratinocytes in Human Skin Pigmentation
Benito-Martínez, S., Salavessa, L., Raposo, G., Marks, M. S., & Delevoye, C. (2021) · Integrative and Comparative Biology · doi:10.1093/icb/icab094 · Cited by 78 · see citing works
Adaptive redox homeostasis in cutaneous melanoma
Arslanbaeva, L. R., & Santoro, M. M. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101753 · Cited by 85 · see citing works
Ultraviolet radiation-mediated development of cutaneous melanoma: An update
Emri, G., Paragh, G., Tósaki, Á., Janka, E. A., Kollár, S., Hegedűs, C., Gellén, E., Horkay, I., Koncz, G., & Remenyik, É. (2018) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2018.06.005 · Cited by 83 · see citing works
Endogenous Photosensitizers in Human Skin.
Bastos, E., Quina, F., & Baptista, M. S. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.2c00787 · Cited by 69 · see citing works
Allegra, A., Pioggia, G., Tonacci, A., Musolino, C., & Gangemi, S. (2020) · Antioxidants · doi:10.3390/antiox9050448 · Cited by 83 · see citing works
“Thus, areas of the genome with a high frequency of adjacent pyrimidines are considered “UV hotspots” and show high rates of C > T and CC > TT “UV signature” mutations [14].”
BackgroundBrouwer, N. J., Verdijk, R. M., Heegaard, S., Marinkovic, M., Esmaeli, B., & Jager, M. J. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100971 · Cited by 78 · see citing works
“Eumelanin has protective effects on melanoma formation, by shielding against UV radiation (De Leeuw et al., 2001) and scavenging reactive oxygen species (ROS) and free radicals (Brenner and Hearing, 2008); pheomelanin can be involved in DNA damage via UVA (Premi et al., 2015) and by itself via independent ROS formatio…”
BackgroundInfluentialAll You Need Is Light. Photorepair of UV-Induced Pyrimidine Dimers
Banaś, A. K., Zgłobicki, P., Kowalska, E., Bażant, A., Dziga, D., & Strzałka, W. (2020) · Genes · doi:10.3390/genes11111304 · Cited by 77 · see citing works
“It has been demonstrated that melanin may act in vivo as a photosensitizer [35].”
BackgroundJeayeng, S., Wongkajornsilp, A., Slominski, A. T., Jirawatnotai, S., Sampattavanich, S., & Panich, U. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.05.009 · Cited by 78 · see citing works
“UVB irradiation can cause the loss of cellular integrity, direct damage to DNA and trigger various cellular responses including apoptosis [3] and inflammation [4] in skin cells including melanocytes (MC).”
BackgroundUVA Radiation, DNA Damage, and Melanoma
Jin, S., Padron, F., & Pfeifer, G. P. (2022) · ACS Omega · doi:10.1021/acsomega.2c04424 · Cited by 83 · see citing works
Photoprotection versus photodamage: updating an old but still unsolved controversy about melanin
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NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism
Allouche, J., Rachmin, I., Adhikari, K., Pardo, L. M., Lee, J. H., McConnell, A. M., Kato, S., Fan, S., Kawakami, A., Suita, Y., et al. (2021) · Cell · doi:10.1016/j.cell.2021.06.022 · Cited by 72 · see citing works
“UV radiation can interact photochemically with DNA to form cyclobutane pyrimidine dimers (CPD) and 6,4-photoproducts 10 and can cause the production of reactive oxygen species (ROS) through multiple mechanisms, thereby increasing the risk of developing skin cancer (Premi et al., 2015).”
BackgroundSelf-citationNguyen, T. M. H., Kim, S., & Bark, C. W. (2020) · Journal of Materials Chemistry A · doi:10.1039/d0ta08738f · Cited by 74 · see citing works
Frequent DPH3 promoter mutations in skin cancers
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“It has been recognised for many years that even though melanins are photoprotective they can also be photosenstisers and, therefore, lead to skin damage [34,35].”
BackgroundKim, E., Kang, M., Tschirhart, T., Malo, M. E., Dadachova, E., Cao, G., Yin, J., Bentley, W. E., Wang, Z., & Payne, G. F. (2017) · Biomacromolecules · doi:10.1021/acs.biomac.7b01166 · Cited by 71 · see citing works
Four‐membered cyclic peroxides: Carriers of chemical energy
Bastos, E. L., Farahani, P., Bechara, E. J. H., & Baader, W. J. (2017) · Journal of Physical Organic Chemistry · doi:10.1002/poc.3725 · Cited by 68 · see citing works
Self-citationMalignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling
Slominski, R. M., Kim, T., Janjetović, Z., Brożyna, A. A., Podgórska, E., Dixon, K. M., Mason, R. S., Tuckey, R. C., Sharma, R., Crossman, D. K., et al. (2024) · Cancers · doi:10.3390/cancers16122262 · Cited by 74 · see citing works
Significance of melanin distribution in the epidermis for the protective effect against UV light
Zamudio Díaz, D. F., Busch, L., Kröger, M., Klein, A. L., Lohan, S. B., Mewes, K. R., Vierkotten, L., Witzel, C., Rohn, S., & Meinke, M. C. (2024) · Scientific Reports · doi:10.1038/s41598-024-53941-0 · Cited by 71 · see citing works
Boosting the Optical Absorption of Melanin-like Polymers
Bai, W., Yang, P., Liu, H., et al. (2022) · Macromolecules · doi:10.1021/acs.macromol.2c00506 · Cited by 69 · see citing works
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“parviflora (upper panel), and endolysosomal patch-clamp measurement demonstrating effect of the extract (10 μg/ ml) to block TPC2 stimulated by PI(3,5)P2 (1 μM).”
BackgroundMethodInfluentialSelenomelanin: An Abiotic Selenium Analogue of Pheomelanin
Cao, W., McCallum, N. C., Ni, Q. Z., Li, W., Boyce, H., Mao, H., Zhou, X., Sun, H. R., Thompson, M. P., Battistella, C., et al. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c05573 · Cited by 66 · see citing works
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Effect of ultraviolet radiation on the Nrf2 signaling pathway in skin cells
Ryšavá, A., Vostálová, J., & Svobodová, A. R. (2021) · International Journal of Radiation Biology · doi:10.1080/09553002.2021.1962566 · Cited by 65 · see citing works
de Assis, L. V. M., Moraes, M. N., Cruz‐Machado, S. D. S., & Castrucci, A. M. D. L. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.03.001 · Cited by 62 · see citing works
Kim, J., Hong, A., Kim, Y.-H., et al. (2020) · Theranostics · doi:10.7150/thno.41502 · Cited by 64 · see citing works
“For instance, skin tissue is directly exposed to ultraviolet radiation (UVR), which renders skin tissue highly susceptible to carcinogenesis via somatic mutations through the generation of reactive oxygen and nitrogen species [1].”
Backgroundde Assis, L. V. M., Moraes, M. N., Magalhães-Marques, K. K., & Castrucci, A. M. D. L. (2018) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2018.01.004 · Cited by 64 · see citing works
Shedding a New Light on Skin Aging, Iron- and Redox-Homeostasis and Emerging Natural Antioxidants
Pourzand, C., Albieri, A., & Raczek, N. N. (2022) · Antioxidants · doi:10.3390/antiox11030471 · Cited by 62 · see citing works
“The formation of ‘dark’ CPDs in melanocytes and pigmented skin appear to occur long after UVA irradiation via the chemo-excitation of melanin [94].”
BackgroundHerráiz, C., Martínez‐Vicente, I., & Maresca, V. (2021) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12980 · Cited by 63 · see citing works
“In human melanocytes, exposure to UVR causes chemical excitation of fragments of the pigment melanin, resulting in the formation of additional CPDs (Premi et al., 2015). α- MSH has been shown to protect against the UVR- induced oxidative stress by several pigment- independent mechanisms, including…”
BackgroundInfluentialImpact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin
Kemp, M. G., Spandau, D. F., & Travers, J. B. (2017) · Molecules · doi:10.3390/molecules22030356 · Cited by 62 · see citing works
“UVA is also capable of inducing CPD formation by direct photon absorption [12,13] and via a recently characterized process termed chemiexcitation, in which reactive oxygen and nitrogen species induced by UVA combine to excite electrons in fragments of melanin that ultimately induce CPD production in genomic DNA [14,15…”
BackgroundThe dark side of the light: mechanisms of photocarcinogenesis
Coelho, M. M. V., Matos, T. R., & Apetato, M. (2016) · Clinics in Dermatology · doi:10.1016/j.clindermatol.2016.05.022 · Cited by 60 · see citing works
Lee, V., Bashir, H. M., & Seykora, J. (2017) · Journal of Ophthalmic and Vision Research · doi:10.4103/jovr.jovr_114_17 · Cited by 60 · see citing works
“[32,33] The corneal epithelium lacks features skin possesses to resist UV damage, such as a thicker epithelial layer, stratum corneum, and melanocytes, which all help to mitigate the effects of UV radiation.[34,35] Mallet et al show instead that corneal epithelium appears to repair signature UV‐induced mutations more…”
BackgroundMolecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances
Kim, H. J., & Kim, Y. H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052984 · Cited by 63 · see citing works
Goswami, L., Pandey, R., & Gupta, G. (2020) · Optical Materials · doi:10.1016/j.optmat.2020.109820 · Cited by 58 · see citing works
Hierarchical Micro‐/Nanostructures from Human Hair for Biomedical Applications
Zheng, D., Hong, S., Xu, L., Li, C., Li, K., Cheng, S., & Zhang, X. (2018) · Advanced Materials · doi:10.1002/adma.201800836 · Cited by 57 · see citing works
Stark, M. S., Tan, J.-M., Tom, L. N., et al. (2018) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2018.02.012 · Cited by 58 · see citing works
“This notion is supported by the study by Premi et al. (2015), which described that the many of cyclobutane pyrimidine dimers arise via the breakdown of melanin pigment.”
ResultUltraviolet light and melanoma
Craig, S., Earnshaw, C. H., & Virós, A. (2018) · The Journal of Pathology · doi:10.1002/path.5039 · Cited by 54 · see citing works
“A novel mechanism by which UVA can induce any type of CPD formation has been recently suggested, and, paradoxically, this depends on melanin [52].”
BackgroundRajkumar, S., & Watson, I. R. (2016) · British Journal of Cancer · doi:10.1038/bjc.2016.195 · Cited by 57 · see citing works
“However, recent studies have shown that UVA can induce C4T signature mutations through a reactive oxygen species (ROS)-dependent mechanism involving both the the photoprotective black eumelanin and the phototoxic red pheomelanin (Noonan et al, 2012; Premi et al, 2015).”
BackgroundThe Dark Side of Melanin Secretion in Cutaneous Melanoma Aggressiveness
Cabaço, L. C., Tomás, A., Pojo, M., & Barral, D. C. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.887366 · Cited by 56 · see citing works
“melanin and contribute to mutations triggering CM cell immortalization and carcinogenesis (33).”
BackgroundInfluentialGrigalavicius, M., Moan, J. E., Dahlback, A., & Juzeniene, A. (2015) · International Journal of Dermatology · doi:10.1111/ijd.13065 · Cited by 57 · see citing works
Dong, M., Zheng, X., Li, Q., et al. (2024) · Materials Today · doi:10.1016/j.mattod.2024.03.004 · Cited by 55 · see citing works
Prevention of DNA damage in human skin by topical sunscreens
Olsen, C. M., Wilson, L. F., Green, A. C., Biswas, N., Loyalka, J., & Whiteman, D. C. (2017) · Photodermatology Photoimmunology & Photomedicine · doi:10.1111/phpp.12298 · Cited by 54 · see citing works
“For that study, biopsies were taken 24 h and 14 days following UVR exposure, which covers the time period during which ‘dark CPDs’ can form, putatively as a result of UVA-induced reactive oxygen and nitrogen species (28).”
Background
- Authors
- Premi, S., Wallisch, S., Mano, C. M., Weiner, A. B., Bacchiocchi, A., Wakamatsu, K., Bechara, E. J. H., Halaban, R., Douki, T., & Brash, D. E.
- Affiliations
- Yale University (US)
- Universidade de São Paulo (BR)
- Fujita Health University (JP)
- Yale Cancer Center (US)
- Université Joseph Fourier (FR)
- Corresponding author
- Bechara, Etelvino J. H.
- Douki, Thierry
- Brash, Douglas E.
- ORCID
- Venue
- Science
- Published
- 2015-02-20
- Volume
- 347
- Issue
- 6224
- Pages
- 842-847
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4432913
- OpenAlex
- W2093971029
- Semantic Scholar
- 26c414be169fcb7ec90f18696beb5729a3815347
- Cited by
- 550
- References
- 39
- Citations by year
- 2026: 34 · 2025: 47 · 2024: 43 · 2023: 43 · 2022: 54 · 2021: 66 · 2020: 46 · 2019: 45 · 2018: 45 · 2017: 46 · 2016: 53 · 2015: 24 · 2014: 3 · 2013: 1
- FWCI
- 38.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- Department of Defense CDMRP (CA093473P1, CA093473)
- University of Veterinary Medicine, Vienna
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
- FAPESP (06/56530-4)
- NIH (P50 CA121974, P30 DK34989)
- Topics
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Photochemistry and Electron Transfer Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- melanin, chemiexcitation, cyclobutane pyrimidine dimers, DNA photoproducts, melanoma, UVA, melanocytes, triplet state, reactive oxygen species, reactive nitrogen species, tanning beds
- MeSH terms
- Animals, Cells, Cultured, Cytosine, DNA, DNA Damage, Energy Transfer, Humans, Melanins, Melanocytes, Melanoma, Mice, Inbred C57BL, Mutation, Neoplasms, Radiation-Induced, Pyrimidine Dimers, Skin Neoplasms, Sunlight, Thymine, Ultraviolet Rays, Mutagenesis, Photons, Receptor, Melanocortin, Type 1, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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