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Article
Nature Medicine  3, 510 - 514 (1997)
doi:10.1038/nm0597-510

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

Honnavara N. Ananthaswamy, Susan M. Loughlin, Patricia Cox, Randall L. Evans, Stephen E. Ullrich & Margaret L. Kripke

Department of Immunology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 178, Houston, Texas 77030, USA

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.

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). | PubMed  | ISI |
  2. Urbach, F. Evidence and epidemiology of ultraviolet-induced cancers in man. Natl. Cancer Inst. Monogr. 50, 5−10 (1978). | PubMed  |
  3. Scotto, J. & Fears, T.R. Skin cancer epidemiology: Research needs. Natl. Cancer Inst. Monogr. 50, 169−177 (1978). | PubMed  |
  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). | PubMed  | ChemPort |
  5. Rady, P., Scinicariello, F., Wagner, R.F. & Tyring, S.K. p53 mutations in basal Cell carcinomas. Cancer Res. 52, 3804−3806 (1992). | PubMed  | ISI | ChemPort |
  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). | ChemPort |
  7. Blum, H.F. Carcinogenesis by Ultraviolet Light. (Princeton Univ. Press, Princeton, NJ, 1959.
  8. Urbach, F. The Biologic Effects of Ultraviolet Radiation. (Pergamon, New York, 1969).
  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). | PubMed  | ISI | ChemPort |
  10. Forbes, P.O. Experimental photocarcinogenesis: An overview. J. Invest. Dermatol. 77, 139−143 (1981). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  12. Gilchrest, B.A. Actinic injury. Anna. Rev. Med. 41, 199−210 (1990). | Article | ChemPort |
  13. Young, A.R. Cumulative effects of ultraviolet radiation on the skin: Cancer and photoaging. Semin. Dermatol. 9, 25−31 (1990). | PubMed  | ISI | ChemPort |
  14. Kligman, L.H. & Kligman, A.M. The nature of photoaging: Its prevention and repair. Photodermatology 3, 215−227 (1986). | PubMed  | ISI | ChemPort |
  15. Kripke, M.L. Immunological effects of ultraviolet radiation. J. Dermatol. 18, 429−433 (1991). | PubMed  | ChemPort |
  16. Lowe, N.J. & Breedings, J. Evaluation of sunscreen protection by measurement of epidermal DNA synthesis. J. Invest. Dermatol. 74, 181−182, 1980. | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ChemPort |
  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 Mexorylright arrow SX. Photochem. Photobiol. 55, 549−560 (1992). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  24. Fourtanier, A. Mexorylright arrow SX protects against solar-simulated UVR-induced photocarcinogenesis. Photochem. Photobiol. 64, 688−693 (1996). | PubMed  | ISI | ChemPort |
  25. Kligman, A.H., Akin, F.J. & Kligman, A.M. Sunscreens prevent ultraviolet photocarcinogenesis. J Am. Acad. Dermatol. 3, 30−35 (1980). | PubMed  | ISI |
  26. Levine, A.J., Momand, J. & Finlay, C.A., The p53 tumor suppressor gene Nature 351, 453−456 (1991). | Article | PubMed  | ISI | ChemPort |
  27. Vogelstein, B. & Kinzler, K.W.. p53 function and dysfunction. Cell 70, 523−526 (1992). | Article | PubMed  | ISI | ChemPort |
  28. Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C.C. p53 mutations in human cancers. Science 253, 49−53 (1991). | PubMed  | ISI | ChemPort |
  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). | ChemPort |
  30. Moles, J.-P. et al. p53 gene mutations in human epithelial skin cancers. Oncogene 8, 583−588 (1993). | PubMed  | ISI | ChemPort |
  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). | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ChemPort |
  34. Nataraj, A.J., Trent, J.C. & Ananthaswamy, H.N. pS3 gene mutations and photocarcinogenesis. Photochem. Photobiol. 62, 165−177 (1995).
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ChemPort |
  39. Ziegler, A. et al. Sunburn and p53 in the onset of skin cancer. Nature 372, 773−776 (1994). | Article | PubMed  | ISI | ChemPort |
  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 | PubMed  | ISI | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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 | PubMed  | ChemPort |
  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 | PubMed  | ChemPort |
  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). | PubMed  | ISI | ChemPort |
  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). | PubMed  | ChemPort |
  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 | PubMed  | ChemPort |
  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 | PubMed  | ChemPort |
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ISSN: 1078-8956
EISSN: 1546-170X
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