Cyclobutane pyrimidine dimers are photosensitised by carprofen plus UVA in human HaCaT cells
Abstract
Every year in the UK about 75,000 cases of non-melanoma skin cancer (NMSC) are registered, and about 9500 people are diagnosed with cutaneous melanoma (CM). The main risk factor for these cancers is exposure to sunlight. The effects of light on skin are wavelength dependent, with wavelengths in the UVB waveband (280-315 nm) being the most carcinogenic. UVB is directly absorbed by DNA, producing dimeric pyrimidine photoproducts including cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimodone photoproducts (6-4PP). However UVA (315-400 nm) can also produce CPD, induce skin tumours in mice, and has been shown to be mutagenic in cell culture. Although the precise role of UVA in human skin cancer remains to be elucidated, it comprises the major portion of solar UV radiation, transmits through window glass and can be delivered in high doses from tanning lamps. Non-steroidal anti-inflammatory drugs (NSAIDs), in particular the 2-aryl propionic acid derivatives, are a well-documented group of photosensitising chemicals producing clinical phototoxic and photoallergic reactions. We have used carprofen, a model compound from this group to see if it could amplify the effects of UVA and contribute to the formation of CPD by UVA. Preliminary work has shown that carprofen combined with low doses of UVA (lambda(max): 365 nm; 5 J/cm(2)) can produce both strand breaks (SB) and CPD in human skin or blood cells. CPD were detected indirectly by both an immunofluorescence method and as T4 endonuclease V sensitive sites in the comet assay. These findings show that compounds other than fluoroquinolones and psoralen derivatives may contribute to CPD formation in skin cells in combination with UVA.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Carprofen UVA sensitizes the formation of cyclobutane pyrimidine dimers in the DNA of human keratinocyte (HaCaT) cell lines.
“Carprofen, a nonsteroidal antiinflammatory drug, is also able to UVA sensitize the formation of CPDs in the DNA of human keratinocyte (HaCaT) cell lines as inferred from immunofluorescence detection and application of a modified version of the alkaline comet assay involving the use of T4 endonuclease V (152).”
From Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup> (2012) · cites this paper as [152]
Cites
Free radicals in biology and medicine
Gutteridge, J. M. C. (1991) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(91)90478-o · Cited by 17,178 · see citing works
Free radicals in biology and medicine
Halliwell, B. B., & Gutteridge, J. M. C. (1985) · Journal of Free Radicals in Biology & Medicine · doi:10.1016/0748-5514(85)90140-0 · Cited by 2,931 · see citing works
Mouret, S., Baudouin, C., Charveron, M., Favier, A., Cadet, J., & Douki, T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604213103 · Cited by 684 · see citing works
Buckman, S. (1998) · Carcinogenesis · doi:10.1093/carcin/19.5.723 · Cited by 593 · see citing works
Agar, N., Halliday, G. M., Barnetson, R. S., Ananthaswamy, H. N., Wheeler, M., & Jones, A. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401141101 · Cited by 530 · see citing works
Ultraviolet A and melanoma: A review
Wang, S. Q., Setlow, R. B., Berwick, M., Polsky, D., Marghoob, A. A., Kopf, A. W., & Bart, R. S. (2001) · Journal of the American Academy of Dermatology · doi:10.1067/mjd.2001.114594 · Cited by 454 · see citing works
The risk of melanoma in association with long-term exposure to PUVA
Stern, R. S. (2001) · Journal of the American Academy of Dermatology · doi:10.1067/mjd.2001.114576 · Cited by 372 · see citing works
Risk of Squamous Cell Carcinoma and Methoxsalen (Psoralen) and UV-A Radiation (PUVA)
Stern, R. S., & Lunder, E. J. (1998) · Archives of Dermatology · doi:10.1001/archderm.134.12.1582 · Cited by 231 · see citing works
Rochette, P. J. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg402 · Cited by 231 · see citing works
Tice, R. R., Andrews, P. W., HIRAI, O., & Singh, N. P. (1991) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-5877-0_17 · Cited by 208 · see citing works
An, K. P., Athar, M., Tang, X., Katiyar, S. K., Russo, J., Beech, J. A., Aszterbaum, M., Kopelovich, L., Epstein, E. H., Mukhtar, H., et al. (2002) · Photochemistry and Photobiology · doi:10.1562/0031-8655(2002)0760073ceimah2.0.co2 · Cited by 193 · see citing works
Photopatch testing: The 5-year experience of the German, Austrian, and Swiss Photopatch Test Group
Hölzle, E., Neumann, N. J., Hausen, B. M., Bernhard Przybilla, A., Schauder, S., Hönigsmann, H., Bircher, A. J., & Plewig, G. (1991) · Journal of the American Academy of Dermatology · doi:10.1016/0190-9622(91)70175-2 · Cited by 180 · see citing works
The interaction with tubulin of a series of stilbenes based on combretastatin A-4
Woods, J. A., Hadfield, J. A., Pettit, G. R., Fox, B. W., & McGown, A. T. (1995) · British Journal of Cancer · doi:10.1038/bjc.1995.138 · Cited by 175 · see citing works
Self-citationAnimal Cell Culture: A Practical Approach
Raxworthy, M. (1987) · Biochemical Education · doi:10.1016/0307-4412(87)90173-7 · Cited by 159 · see citing works
Besaratinia, A., Synold, T. W., Chen, H.-H., Chang, C., Xi, B., Riggs, A. D., & Pfeifer, G. P. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502311102 · Cited by 156 · see citing works
Use of photosensitising diuretics and risk of skin cancer: a population-based case–control study
Jensen, A. Ø., Thomsen, H. F., Engebjerg, M. C., Olesen, A. B., Sørensen, H. T., & Karagas, M. R. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604686 · Cited by 155 · see citing works
Quinolone antibacterials: A new class of photochemical carcinogens
Mäkinen, M. J., Forbes, P. D., & Stenbäck, F. (1997) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/s1011-1344(96)07425-8 · Cited by 112 · see citing works
MACKENZIE, L. A., & Frain-Bell, W. (1973) · British Journal of Dermatology · doi:10.1111/j.1365-2133.1973.tb02972.x · Cited by 103 · see citing works
Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs in canine blood
Streppa, H. K., Jones, C. J., & Budsberg, S. C. (2002) · American Journal of Veterinary Research · doi:10.2460/ajvr.2002.63.91 · Cited by 102 · see citing works
Temporal changes in the incidence of malignant melanoma: Explanation from action spectra
Setlow, R. B., & Woodhead, A. D. (1994) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(94)90310-7 · Cited by 87 · see citing works
Ikehata, H., Kawai, K., Komura, J.-I., Sakatsume, K., Wang, L., Imai, M., Higashi, S., Nikaido, O., Yamamoto, K., Hieda, K., et al. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.61 · Cited by 79 · see citing works
Rünger, T. M. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700988 · Cited by 74 · see citing works
The Clinical Pharmacology of Cyclooxygenase-2–Selective and Dual Inhibitors
Clark, T. P. (2006) · Veterinary Clinics of North America Small Animal Practice · doi:10.1016/j.cvsm.2006.07.001 · Cited by 59 · see citing works
Stern, R. S. (1998) · Toxicology Letters · doi:10.1016/s0378-4274(98)00237-9 · Cited by 57 · see citing works
Joosse, A., Koomen, E. R., Casparie, M. K., Herings, R. M. C., Guchelaar, H., & Nijsten, T. E. C. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2009.201 · Cited by 54 · see citing works
Occupational carprofen photoallergic contact dermatitis
Kerr, A. C., Muller, F., Ferguson, J., & Dawe, R. S. (2008) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2008.08847.x · Cited by 53 · see citing works
Self-citationAnimal cell culture; a practical approach
(1993) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(93)90058-c · Cited by 51 · see citing works
Measurement of Menadione-Mediated DNA Damage in Human Lymphocytes Using the Comet Assay
Woods, J. A., Young, A. J., Gilmore, I. T., Morris, A., & Bilton, R. F. (1997) · Free Radical Research · doi:10.3109/10715769709097790 · Cited by 48 · see citing works
Self-citationKaragas, M. R., Stukel, T. A., Umland, V., Tsoukas, M. M., Mott, L. A., Sørensen, H. T., Jensen, A. Ø., Nelson, H. H., Spencer, S. K., Perry, A. E., et al. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700934 · Cited by 46 · see citing works
Boscá, F., Encinas, S., Heelis, P. F., & Miranda, M. A. (1997) · Chemical Research in Toxicology · doi:10.1021/tx9700376 · Cited by 46 · see citing works
Phototoxicity of non-steroidal anti-inflammatory drugs: in vitro studies with visible light.
Becker, L., Eberlein-König, B., & Przybilla, B. (1996) · Acta Dermato Venereologica · doi:10.2340/0001555576337340 · Cited by 45 · see citing works
Photosensibilisation au carprofène (Imadyl ® ), un nouvel anti-inflammatoire non stéroïdien
Mérot, Y., Harms, M., & Saurat, J. (2009) · Dermatologica · doi:10.1159/000249894 · Cited by 41 · see citing works
Narlawar, R., Pérez‐Revuelta, B. I., Haass, C., Steiner, H., Schmidt, B., & Baumann, K. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm0610200 · Cited by 36 · see citing works
[Photosensitizing properties of nonsteroidal antirheumatic drugs in the photopatch test].
Bernhard Przybilla, A., Ring, J., Schwab, U., Galosi, A., Dorn, M., & Braun‐Falco, O. (1987) · PubMed · Cited by 35 · see citing works
Traynor, N. J., Beattie, P. E., Ibbotson, S. H., Moseley, H., Ferguson, J., & Woods, J. A. (2005) · Toxicology Letters · doi:10.1016/j.toxlet.2005.03.012 · Cited by 31 · see citing works
Self-citationWalker, S. L., Ead, R. D., & Beck, M. H. (2006) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2005.07096.x · Cited by 30 · see citing works
Population reference intervals for minimal erythemal doses in monochromator phototesting
Moseley, H., Naasan, H., Dawe, R. S., Woods, J. A., & Ferguson, J. (2009) · Photodermatology Photoimmunology & Photomedicine · doi:10.1111/j.1600-0781.2009.00391.x · Cited by 28 · see citing works
Self-citationMolecular mechanism of drug photosensitization 4. Photohemolysis sensitized by carprofen
Guidi, G. D., Chillemi, R., Costanzo, L. L., Giuffrida, S., & Condorelli, G. (1993) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/1011-1344(93)80021-z · Cited by 27 · see citing works
Traynor, N. J., & Gibbs, N. K. (1999) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1999.tb08308.x · Cited by 26 · see citing works
Self-citationThe etiology of sunlight‐induced melanoma in Xiphophorus hybrid fish
Mitchell, D. L., Paniker, L., Sánchez, G., Trono, D., & Nairn, R. S. (2007) · Molecular Carcinogenesis · doi:10.1002/mc.20341 · Cited by 26 · see citing works
Trzcionka, J., Lhiaubet‐Vallet, V., Paris, C., Belmadoui, N., Climent, M. J., & Miranda, M. A. (2007) · ChemBioChem · doi:10.1002/cbic.200600394 · Cited by 24 · see citing works
Agapakis‐Causse, C., Boscá, F., Castell, J. V., Hernández, D., Marin, M. L., Marrot, L., & Miranda, M. A. (2000) · Photochemistry and Photobiology · doi:10.1562/0031-8655(2000)0710499tapdtn2.0.co2 · Cited by 23 · see citing works
Measurement of daylight UVA in Glasgow
Moseley, H., Davison, M., & Mackie, R. M. (1983) · Physics in Medicine and Biology · doi:10.1088/0031-9155/28/5/011 · Cited by 21 · see citing works
Self-citationSkin Cancer after PUVA Treatment for Psoriasis
Morgan, R. W. (1979) · New England Journal of Medicine · doi:10.1056/nejm197909063011014 · Cited by 21 · see citing works
In vitro studies on DNA-photosensitization by different drug stereoisomers
Lhiaubet‐Vallet, V., Sarabia, Z., Hernández, D., Castell, J. V., & Miranda, M. A. (2003) · Toxicology in Vitro · doi:10.1016/s0887-2333(03)00108-5 · Cited by 16 · see citing works
Effect of Cyclobutane Pyrimidine Dimers on Apoptosis Induced by Different Wavelengths of UV
Nishigaki, R., Mitani, H., Tsuchida, N., & Shima, A. (1999) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1999.tb07993.x · Cited by 16 · see citing works
Skin cancer after PUVA treatment for psoriasis.
Stern, R. S., La, T., Ja, P., & Fitzpatrick, T. B. (1979) · PubMed · Cited by 11 · see citing works
[Photoallergic reaction to carprofen].
Hoting, E., & Kh, S. (1984) · PubMed · Cited by 8 · see citing works
Kossodo, S. C., Wong, W., Simon, G., & Kochevar, I. E. (2004) · Photochemistry and Photobiology · doi:10.1562/0031-8655(2004)79 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions<sup>†</sup>
Cadet, J., Mouret, S., Ravanat, J., & Douki, T. (2012) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2012.01200.x · Cited by 300 · 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
Swalwell, H., Latimer, J., Haywood, R. M., & Birch‐Machin, M. A. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.11.019 · Cited by 152 · see citing works
UVA1 induces cyclobutane pyrimidine dimers but not 6-4 photoproducts in human skin in vivo
Tewari, A., Sarkany, R. P., & Young, A. R. (2012) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.283 · Cited by 141 · see citing works
DNA damage spectra induced by photosensitization
Epe, B. (2011) · Photochemical & Photobiological Sciences · doi:10.1039/c1pp05190c · Cited by 133 · see citing works
Photosensitised pyrimidine dimerisation in DNA
Cuquerella, M. C., Lhiaubet‐Vallet, V., Boscá, F., & Miranda, M. A. (2011) · Chemical Science · doi:10.1039/c1sc00088h · Cited by 109 · 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
UVA1 is skin deep: molecular and clinical implications
Tewari, A., Grage, M. M.-L., Harrison, G. I., Sarkany, R., & Young, A. R. (2012) · Photochemical & Photobiological Sciences · doi:10.1039/c2pp25323b · Cited by 93 · see citing works
The enzyme-modified comet assay: Past, present and future
Muruzabal, D., Collins, A. R., & Azqueta, A. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111865 · Cited by 85 · 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
Voriconazole-induced photosensitivity: photobiological assessment of a case series of 12 patients
Haylett, A. K., Felton, S. J., Denning, D. W., & Rhodes, L. E. (2012) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2012.11196.x · Cited by 56 · see citing works
Sun Exposure and Melanoma, Certainties and Weaknesses of the Present Knowledge
Arisi, M., Zane, C., Caravello, S., Rovati, C., Zanca, A., Venturini, M., & Calzavara‐Pinton, P. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00235 · Cited by 50 · see citing works
Silymarin: Friend or Foe of UV Exposed Keratinocytes?
Fidrus, E., Ujhelyi, Z., Fehér, P. S., Hegedűs, C., Janka, E. A., Paragh, G., Vasas, G., Bácskay, I., & Remenyik, É. (2019) · Molecules · doi:10.3390/molecules24091652 · Cited by 13 · see citing works
Formation of DNA strand breaks in peripheral lymphocytes of rats after exposure to natural sunlight.
Rodrigues‐Junior, D. M., Melo, A. A. D. C., da Silva, B. B., & Lopes‐Costa, P. V. (2012) · PubMed · doi:10.3967/0895-3988.2012.02.018 · Cited by 4 · see citing works
Rodríguez‐Muñiz, G. M., Gomez‐Mendoza, M., Miro, P., García‐Orduña, P., Sastre, G., Miranda, M. A., & Marin, M. L. (2022) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.2c00942 · Cited by 2 · see citing works
Wang, J., Yano, S., Xie, K., Ohata, Y., & Hara, T. (2022) · Genes · doi:10.3390/genes13060974 · Cited by 2 · see citing works
Dikici, İ. H., Özpolat, S. G., Çelık, H., & Koçyiğit, A. (2025) · Medical Research Reports · doi:10.55517/mrr.1551440
Drug‐Sensitized Triplet States Generation in DNA
Montero‐Galán, C., Rodríguez‐Muñiz, G. M., & Lhiaubet‐Vallet, V. (2026) · doi:10.1002/9783527850372.ch5
- Authors
- Robinson, K. S., Traynor, N. J., Moseley, H., Ferguson, J., & Woods, J. A.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Woods, J.A.
- Venue
- Toxicology in Vitro
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 24
- Issue
- 4
- Pages
- 1126-1132
- ISSN
- 0887-2333 (ISSN-L)
- OpenAlex
- W2003304403
- Cited by
- 18
- References
- 49
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2012: 4
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology in Vitro (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- cyclobutane pyrimidine dimers, carprofen, UVA, photosensitization, nonsteroidal anti-inflammatory drugs, DNA strand breaks, T4 endonuclease V, HaCaT keratinocytes, non-melanoma skin cancer, cutaneous melanoma, phototoxicity, photomutagenesis
- MeSH terms
- Anti-Inflammatory Agents, Non-Steroidal, Carbazoles, Humans, Pyrimidine Dimers, Ultraviolet Rays, Photosensitizing Agents, U937 Cells, DNA Breaks
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
