p53 protects against skin cancer induction by UV-B radiation

To assess the role of the p53 tumor suppressor gene in skin carcinogenesis by UV radiation, mice constitutively lacking one or both copies of the func tional p53 gene were compared to wild-type mice for their susceptibility to UV carcinogenesis. Heterozygous mice showed greatly increased susceptibili ty to skin cancer induction, and homozygous p53 knockout mice mere even mor e susceptible, Accelerated tumor development in the heterozygotes was not a ssociated with loss of the remaining wild-type allele of p53, as reported f or tumors induced by other carcinogens, but in many cases was associated wi th UV-induced mutations in p53, Tumors arose on the ears and dorsal skin of mice of all three genotypes, and homozygous knockout mice also developed o cular tumors, mainly melanomas, Skin tumors in the p53 knockout mice were p redominately squamous cell carcinomas and were associated with premalignant lesions resembling actinic keratoses, whereas those in the heterozygous an d wild-type mice were mainly sarcomas, These results demonstrate the import ance of p53 in protecting against UV-induced cancers, particularly in the e ye and epidermis.