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Sunlight and skin cancer: Inhibition of p53 mutations in UV-irradiated mouse skin by sunscreens

Abstract

UV-induced mutations in the p53 tumor suppressor gene play an essential role in skin cancer development. We report here that such mutations can be detected in UV-irradiated mouse skin months before the gross appearance of skin tumors. Application of SPF-15 sunscreens to mouse skin before each UV irradiation nearly abolished the frequency of p53 mutations. These results indicate that p53 mutation is an early event in UV skin carcinogenesis and that inhibition of this event may serve as an early end point for assessing protective measures against skin cancer development.

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References

  1. Rowe, E., Carroll, R.J. & Day, C.L. Prognostic factors for local recurrence, metastasis, and survival rates in squamous Cell carcinoma of the skin, ear, and lip. J. Am. Acad. Dermatol. 26, 976–990 (1992).

    Article  CAS  Google Scholar 

  2. Urbach, F. Evidence and epidemiology of ultraviolet-induced cancers in man. Natl. Cancer Inst. Monogr. 50, 5–10 (1978).

    Google Scholar 

  3. Scotto, J. & Fears, T.R. Skin cancer epidemiology: Research needs. Natl. Cancer Inst. Monogr. 50, 169–177 (1978).

    Google Scholar 

  4. Brash, D.E. et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous Cell carcinoma. Proc. Natl. Acad. Sci. USA 88, 10124–10128 (1991).

    Article  CAS  Google Scholar 

  5. Rady, P., Scinicariello, F., Wagner, R.F. & Tyring, S.K. p53 mutations in basal Cell carcinomas. Cancer Res. 52, 3804–3806 (1992).

    CAS  PubMed  Google Scholar 

  6. Ziegler, A. et al. Mutation hotspots due to sunlight in the p53 gene of non-melanoma skin cancers. Proc. Natl. Acad. Sd. USA 90, 4216–4220 (1993).

    Article  CAS  Google Scholar 

  7. Blum, H.F. Carcinogenesis by Ultraviolet Light. (Princeton Univ. Press, Princeton, NJ, 1959.

    Book  Google Scholar 

  8. Urbach, F. The Biologic Effects of Ultraviolet Radiation. (Pergamon, New York, 1969).

    Google Scholar 

  9. Kripke, M.L., Latency, histology, and antigenicity of tumors induced by ultraviolet light in three inbred mouse strains Cancer Res. 37, 1395–1400 (1977).

    CAS  PubMed  Google Scholar 

  10. Forbes, P.O. Experimental photocarcinogenesis: An overview. J. Invest. Dermatol. 77, 139–143 (1981).

    Article  CAS  Google Scholar 

  11. Parrish, J.A., Jaenicke, K.F., & Anderson, R.R., Erythema and melanogenesis action spectrum of normal human skin. Photochem. Photobiol. 36, 187–191 (1982).

    Article  CAS  Google Scholar 

  12. Gilchrest, B.A. Actinic injury. Anna. Rev. Med. 41, 199–210 (1990).

    Article  CAS  Google Scholar 

  13. Young, A.R. Cumulative effects of ultraviolet radiation on the skin: Cancer and photoaging. Semin. Dermatol. 9, 25–31 (1990).

    CAS  PubMed  Google Scholar 

  14. Kligman, L.H. & Kligman, A.M. The nature of photoaging: Its prevention and repair. Photodermatology 3, 215–227 (1986).

    CAS  Google Scholar 

  15. Kripke, M.L. Immunological effects of ultraviolet radiation. J. Dermatol. 18, 429–433 (1991).

    Article  CAS  Google Scholar 

  16. Lowe, N.J. & Breedings, J. Evaluation of sunscreen protection by measurement of epidermal DNA synthesis. J. Invest. Dermatol. 74, 181–182, 1980.

    Article  CAS  Google Scholar 

  17. Freeman, S.E., Ley, R.D. & Ley, K.D. Sunscreen protection against UV-induced pyrimidine dimers in DNA of human skin in situ. Photodermatology 5, 243–247 (1988).

    CAS  PubMed  Google Scholar 

  18. De Rijcke, S. & Heenen, M. Decrease of ultraviolet-induced DNA injury in human skin by p-aminobenzoic acid esters. Dermatologica 179, 196–199 (1989).

    Article  CAS  Google Scholar 

  19. Fourtanier, A., Labat-Robert, J., Kern, P., Berrebi, C., Cracia, A.M. & Boyer, B. In vivo evaluation of photoprotection against chronic ultraviolet-A irradiation by a new sunscreen Mexoryl→ SX. Photochem. Photobiol. 55, 549–560 (1992).

    Article  CAS  Google Scholar 

  20. Kligman, L.H., Akin, F.J. & Kligman, A.M. Prevention of ultraviolet damage to the dermis of hairless mice by sunscreens. J. Invest. Dermatol. 78, 181–189 (1982).

    Article  CAS  Google Scholar 

  21. Morison, W.L. The effect of a sunscreen containing para-aminobenzoic acid on the systemic immunologic alterations induced in mice by exposure to UVB radiation. J. Invest. Dermatol. 83, 405–408 (1984).

    Article  CAS  Google Scholar 

  22. Wolf, P., Donawho, C.K. & Kripke, M.L. Analysis of the protective effect of different sunscreens on ultraviolet radiation-induced local and systemic suppression of contact hypersensitivity and inflammatory responses in mice. J. Invest. Dermatol. 100, 254–259 (1993).

    Article  CAS  Google Scholar 

  23. Roberts, L.K. et al. Ultraviolet spectral energy differences affect the ability of sunscreen lotions to prevent ultraviolet radiation-induced immunosuppression. Photochem. Photobiol. 63, 874–884 (1996).

    Article  CAS  Google Scholar 

  24. Fourtanier, A. Mexoryl→ SX protects against solar-simulated UVR-induced photocarcinogenesis. Photochem. Photobiol. 64, 688–693 (1996).

    Article  CAS  Google Scholar 

  25. Kligman, A.H., Akin, F.J. & Kligman, A.M. Sunscreens prevent ultraviolet photocarcinogenesis. J Am. Acad. Dermatol. 3, 30–35 (1980).

    Article  CAS  Google Scholar 

  26. Levine, A.J., Momand, J. & Finlay, C.A., The p53 tumor suppressor gene Nature 351, 453–456 (1991).

    Article  CAS  Google Scholar 

  27. Vogelstein, B. & Kinzler, K.W. . p53 function and dysfunction. Cell 70, 523–526 (1992).

    Article  CAS  Google Scholar 

  28. Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C.C. p53 mutations in human cancers. Science 253, 49–53 (1991).

    Article  CAS  Google Scholar 

  29. Pierceall, W.E., Mukhopadhyay, T., Goldberg, L.H., & Ananthaswamy, H.N. Mutations in p53 tumor suppressor gene in human cutaneous squamous Cell carcinomas. Mol. Cardnog. 4, 445–449 (1991).

    Article  CAS  Google Scholar 

  30. Moles, J.-P. et al. p53 gene mutations in human epithelial skin cancers. Oncogene 8, 583–588 (1993).

    CAS  PubMed  Google Scholar 

  31. Dumaz, N., Drougard, C., Sarasin, A., & Daya-Crosjean, L. Specific UV-induced mutation spectrum in the p53 gene of skin tumors in DNA repair deficient xeroderma pigmentosum patients. Proc. Natl. Acad. Sd. USA 90, 10529–10533 (1993).

    Article  CAS  Google Scholar 

  32. Sato, M., Nishigori, C., Zghal, M., Yagi, T. & Takebe, H. Ultraviolet-specific mutations in the p53 gene in skin tumors in xeroderma pigmentosum patients. Cancer Res. 53, 2944–2946 (1993).

    CAS  PubMed  Google Scholar 

  33. Van der Riet, P. et al. Progression of basal Cell carcinoma through loss of chromosome 9q and inactivation of a single p53 allele. Cancer Res. 54, 25–27 (1994).

    CAS  Google Scholar 

  34. Nataraj, A.J., Trent, J.C. & Ananthaswamy, H.N. pS3 gene mutations and photocarcinogenesis. Photochem. Photobiol. 62, 165–177 (1995).

    Article  Google Scholar 

  35. Kress, S. et al. Carcinogen-specific mutational pattern in the pS3 gene in ultraviolet B radiation-induced squamous Cell carcinomas of mouse skin. Cancer Res. 52, 6400–6403 (1992).

    CAS  PubMed  Google Scholar 

  36. Kanjilal, S., Pierceall, W.E., Cummings, K.K., Kripke, M.L. & Ananthaswamy, H.N. High frequency of pS3 mutations in ultraviolet radiation-induced murine skin tumors: Evidence for strand bias and tumor heterogeneity. Cancer Res. 53, 2961–2964 (1993).

    CAS  PubMed  Google Scholar 

  37. Campbell, C., Quinn, A.C., Ro, Y.S., Angus, B. & Rees, J.L. p53 mutations are common and early events that precede tumor invasion in squamous Cell neoplasia of the skin. J. Invest. Dermatol. 100, 746–748 (1993).

    Article  CAS  Google Scholar 

  38. Nakazawa, H. et al. UV and skin cancer: Specific p53 gene mutation in normal skin as a biologically relevant exposure measurement. Proc. Natl. Acad. Sci. USA 91, 360–364 (1994).

    Article  CAS  Google Scholar 

  39. Ziegler, A. et al. Sunburn and p53 in the onset of skin cancer. Nature 372, 773–776 (1994).

    Article  CAS  Google Scholar 

  40. Nelson, M.A. et al. Analysis of p53 gene in human precancerous actinic keratosis lesions and squamous Cell cancers. Cancer Lett. 85, 23–29 (1994).

    Article  CAS  Google Scholar 

  41. Kanjilal, S. et al. p53 mutations in nonmelanoma skin cancer of the head and neck: Molecular evidence for field cancerization. Cancer Res. 55, 3604–3609 (1995).

    CAS  PubMed  Google Scholar 

  42. Berg, R.J.W. et al. Early p53 alterations in mouse skin carcinogenesis by UVB radiation: Immunohistochemical detection of mutant p53 protein in clusters of preneo-plastic epidermal Cells. Proc. Natl. Acad. Sci. USA 93, 274–278 (1996).

    Article  CAS  Google Scholar 

  43. Jonason, A.S. et al. Frequent clones of p53-mutated keratinocytes in normal human skin. Proc. Natl. Acad. Sci. USA 93, 14025–14029 (1996).

    Article  CAS  Google Scholar 

  44. Ren, Z.P. et al. Human epidermal cancer and accompanying precursors have identical p53 mutations different from p53 mutations in adjacent areas of clonally expanded non-neoplastic keratinocytes. Oncogene 12, 765–773 (1996).

    CAS  PubMed  Google Scholar 

  45. Drobetsky, E.A., Turcotte, J. & Chateauneuf, A. A role for ultraviolet A in solar muta-genesis. Proc. Natl. Acad. Sci. USA 92, 2350–2354 (1995).

    Article  CAS  Google Scholar 

  46. Sage, E. et al. Mutagenic specificity of solar UV light in nucleotide excision repair-deficient rodent Cells. Proc. Natl. Acad. Sci. USA 93, 176–180 (1996).

    Article  CAS  Google Scholar 

  47. International Cosmetic Ingredient Dictionary, 6th edn. (Cosmetic, Toiletry, and Fragrance Association, Washington, DC, 1995).

  48. Nataraj, A.J., Black, H.S. & Ananthaswamy, H.N. Signature p53 mutation at DNA cross-linking sites in 8-methoxypsoralen and ultraviolet A (PUVA)-induced murine skin cancers. Proc. Natl. Acad. Sci. USA 93, 7961–7965 (1996).

    Article  CAS  Google Scholar 

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Ananthaswamy, H., Loughlin, S., Cox, P. et al. Sunlight and skin cancer: Inhibition of p53 mutations in UV-irradiated mouse skin by sunscreens. Nat Med 3, 510–514 (1997). https://doi.org/10.1038/nm0597-510

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