Inhibition of UV-induced p53 mutations by sunscreens: implications for skin cancer prevention.
Ultraviolet (UV) radiation is a potent human carcinogen and it induces skin cancer in experimental animals. Recent studies have shown that unique mutations in the p53 tumor suppressor gene contribute to the development of human and mouse UV-induced skin cancers. Such mutations are also found in sun-damaged skin and actinic keratosis, suggesting that p53 mutations arise early during UV skin carcinogenesis. Our studies have shown that p53 mutations can be detected in UV-irradiated mouse skin months before the gross appearance of skin tumors, suggesting that p53 mutations can serve as a surrogate early biologic endpoint in skin cancer prevention studies. Indeed, application of sun protection factor 15 sunscreens to mouse skin before each UV irradiation resulted in an 88-92% reduction in the number of p53 mutations. Because p53 mutations represent an early essential step in photocarcinogenesis, these results imply that inhibition of this event may protect against skin cancer development.
Ananthaswamy
H N
HN
Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Loughlin
S M
SM
Ullrich
S E
SE
Kripke
M L
ML
D000818:Animals; D006801:Humans; D051379:Mice; D009154:Mutation / Q000187:drug effects* / Q000528:radiation effects; D012867:Skin / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000235:genetics / Q000517:prevention & control*; D013473:Sunscreening Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014466:Ultraviolet Rays
D013473:Sunscreening Agents; D016159:Tumor Suppressor Protein p53