Cited by 435Skin Protection and AgingDNA Repair MechanismsCarcinogens and Genotoxicity Assessment

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Formation of UV-induced DNA damage contributing to skin cancer development

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Cadet, Jean, Douki, Thierry·2018·Photochemical & Photobiological Sciences

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Abstract

UV-induced DNA damage plays a key role in the initiation phase of skin cancer. When left unrepaired or when damaged cells are not eliminated by apoptosis, DNA lesions express their mutagneic properties, leading to the activation of proto-oncogene or the inactivation of tumor suppression genes. The chemical nature and the amount of DNA damage strongly depend on the wavelength of the incident photons. The most energetic part of the solar spectrum at the Earth's surface (UVB, 280-320 nm) leads to the formation of cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (64PPs). Less energetic but 20-times more intense UVA (320-400 nm) also induces the formation of CPDs together with a wide variety of oxidatively generated lesions such as single strand breaks and oxidized bases. Among those, 8-oxo-7,8-dihydroguanine (8-oxoGua) is the most frequent since it can be produced by several mechanisms. Data available on the respective yield of DNA photoproducts in cells and skin show that exposure to sunlight mostly induces pyrimidine dimers, which explains the mutational signature found in skin tumors, with lower amounts of 8-oxoGua and strand breaks. The present review aims at describing the basic photochemistry of DNA and discussing the quantitative formation of the different UV-induced DNA lesions reported in the literature. Additional information on mutagenesis, repair and photoprotection is briefly provided.

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Rutin Protects Fibroblasts from UVA Radiation through Stimulation of Nrf2 Pathway
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The effect of flanking bases on direct and triplet sensitized cyclobutane pyrimidine dimer formation in DNA depends on the dipyrimidine, wavelength and the photosensitizer
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“UVC (200–290 nm), UVB (290–320 nm) and UVA (320– 400 nm) give rise to CPDs via direct excitation of DNA (2,12,14).”
Method
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The key role of UVA-light induced oxidative stress in human Xeroderma Pigmentosum Variant cells
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Radiofrequency Radiation and Cancer
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“target of those type-I photosensitization processes that involve electron abstraction from DNA (30,63,66).”
BackgroundInfluentialSelf-citation
Apoptosis, the only cell death pathway that can be measured in human diploid dermal fibroblasts following lethal UVB irradiation
Gary, A.-S., & Rochette, P. J. (2020) · Scientific Reports · doi:10.1038/s41598-020-75873-1 · Cited by 31
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Rhus coriaria L. Fruit Extract Prevents UV-A-Induced Genotoxicity and Oxidative Injury in Human Microvascular Endothelial Cells
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Biphotonic Ionization of DNA : From Model Studies to Cell
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Self-citation
The sunless tanning agent dihydroxyacetone induces stress response gene expression and signaling in cultured human keratinocytes and reconstructed epidermis
Perer, J., Jandová, J., Fimbres, J., Jennings, E. Q., Galligan, J. J., Hua, A., & Wondrak, G. T. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101594 · Cited by 27
UV irradiation remodels the specificity landscape of transcription factors
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“1A), with the most common being the formation of cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP) at pyrimidine dinucleotides (3).”
Background
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Costa, P. M. (2021) · Ecotoxicology · doi:10.1007/s10646-021-02487-2 · Cited by 28
Contribution of oxidation reactions to photo‐induced damage to cellular DNA
Cadet, J., Angelov, D., Mascio, P. D., & Wagner, J. R. (2024) · Photochemistry and Photobiology · doi:10.1111/php.13990 · Cited by 27
“As an indication of the ability for UVB to induce oxidation reactions in cellular DNA, the formation of 8-oxodGuo was measured initially by HPLC-ECD and subsequently by HPLC-MS/MS (for earlier reviews, see [33,40] and references herein).”
Self-citation
Sunlight Photolysis of Extracellular and Intracellular Antibiotic Resistance Genes tetA and sul2 in Photosensitizer-Free Water
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“However, while UVB-induced dimers involve both thymine and cytosine bases, UVA induces mostly T-containing dimers and does not cause 6-4PPs [3].”
Influential
A chromatin scaffold for DNA damage recognition: how histone methyltransferases prime nucleosomes for repair of ultraviolet light-induced lesions
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Inhibition of α-melanocyte-stimulating hormone-induced melanogenesis and molecular mechanisms by polyphenol-enriched fraction of Tagetes erecta L. flower
Sanjaya, S. S., Park, M. H., Karunarathne, W. A. H. M., Lee, K. T., Choi, Y. H., Kang, C., Lee, M.-H., Jung, M.-J., Ryu, H. W., & Kim, G. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155442 · Cited by 27
Light or Dark Pigmentation of Engineered Skin Substitutes Containing Melanocytes Protects Against Ultraviolet Light-Induced DNA Damage In Vivo
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The Action Spectra of the Visible Light Phototoxicity in Keratinocytes
Tonolli, P. N., Palomino, C. M. V., Junqueira, H. C., & Baptista, M. S. (2022) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2023.112703 · Cited by 29
Purification and Identification of Antioxidant Peptides from Rice Fermentation of Lactobacillus plantarum and Their Protective Effects on UVA−Induced Oxidative Stress in Skin
Mo, Q., You, S., Fu, H., Wang, D., Zhang, J., Wang, C., & Li, M. (2022) · Antioxidants · doi:10.3390/antiox11122333 · Cited by 25
Multiple Dorsal Hand Actinic Keratoses and Squamous Cell Carcinomas: A Unique Presentation following Extensive UV Nail Lamp Use
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Formation of Cyclobutane Pyrimidine Dimers after UVA Exposure (Dark-CPDs) Is Inhibited by an Hydrophilic Extract of Polypodium leucotomos
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“It consists in the formation of CPDs after UVR exposure as a result of chemiexcitation [4].”
Background
Evaluating the polymerization effectiveness and biocompatibility of bio‐sourced, visible light‐based photoinitiator systems
Wendland, R. J., Conway, M. T., & Worthington, K. S. (2024) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37715 · Cited by 22
Encapsulated Activated Grape Seed Extract: A Novel Formulation with Anti-Aging, Skin-Brightening, and Hydration Properties
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Background
Ras-Mediated Activation of NF-κB and DNA Damage Response in Carcinogenesis
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Beyond Traditional Sunscreens: A Review of Liposomal-Based Systems for Photoprotection
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Background
Perovskite quantum dots growth in situ in transparent medium for short wavelength shielding
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“In addition, the overall levels of (6–4) PPs in UV-irradiated chromatin are significantly less than that of CPDs (61).”
Background
Impact of ultraviolet radiation on dermal and epidermal DNA damage in a human pigmented bilayered skin substitute
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“The cyclobutane pyrimidine dimer (CPD) is the most common DNA photolesion (approximatively 70–80%), whereas pyrimidine (6-4) pyrimidone photoproduct (6-4PP) and Dewar photoproduct (DewarPP) account for less than 20% (Cadet & Douki, 2018).”
Background
UVB mutagenesis differs in Nras- and Braf-mutant mouse models of melanoma
Bowman, R. L., Hennessey, R. C., Tallman, D., Weiss, T. J., Crawford, E. R., Murphy, B., Webb, A., Zhang, S., Perle, K. M. D. L., Burd, C. J., et al. (2021) · Life Science Alliance · doi:10.26508/lsa.202101135 · Cited by 25
“These dosing schemes approximate sun exposures of a similar duration, as the UVB to UVA ratio in sunlight is ~1:20, but varies based on season, cloud cover, and latitude (Cadet & Douki, 2018).”
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“Among these, the pyrimidine (6−4) pyrimidone photoproduct (6−4PP) is notable because it is well repaired in cells (4,12,14,15), while the cyclobutane pyrimidine dimer (CPD) that is generated in several-fold greater amount than 6−4PP (16,17) is poorly repaired (18–22).”
Background
Photoprotection by clothing: A review
Boothby‐Shoemaker, W., Mohammad, T. F., Ozog, D., & Lim, H. W. (2022) · Photodermatology Photoimmunology & Photomedicine · doi:10.1111/phpp.12776 · Cited by 21

Authors: Cadet, J., & Douki, T.
Affiliations: Université de Sherbrooke (CA)
Centre National de la Recherche Scientifique (FR)
Corresponding author: Cadet, Jean
Douki, Thierry
ORCID: Cadet, Jean
Douki, Thierry
Venue: Photochemical & Photobiological Sciences
Publisher: Springer Science and Business Media LLC
Published: 2018-12
Volume: 17
Issue: 12
Pages: 1816-1841
ISSN: 1474-905X (ISSN-L)
1474-9092
DOI: 10.1039/c7pp00395a
OpenAlex: W2784555568
Cited by: 435
References: 346
Citations by year: 2026: 47 · 2025: 41 · 2024: 41 · 2023: 62 · 2022: 83 · 2021: 65 · 2020: 49 · 2019: 38 · 2018: 9
FWCI: 6.53
Type: journal article
Language: en
Open access: green
hal.science
Licence: other-oa
www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Photochemical & Photobiological Sciences (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
Topics: Health Sciences › Medicine › Dermatology › Skin Protection and Aging
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords: UV-induced DNA damage, skin cancer, cyclobutane pyrimidine dimers, 6-4 pyrimidone photoproducts, 8-oxo-7,8-dihydroguanine, UVA, UV-B radiation, DNA photoproducts, mutational signatures, DNA repair, photoprotection, apoptosis, proto-oncogenes, tumor suppressor, DNA strand breaks
MeSH terms: Proto-Oncogene Mas, Animals, DNA Damage, DNA Repair, Guanine, Humans, Melanins, Pyrimidine Dimers, Skin Neoplasms, Ultraviolet Rays, DNA Adducts

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Formation of UV-induced DNA damage contributing to skin cancer development

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