UV AND SKIN-CANCER - SPECIFIC P53 GENE MUTATION IN NORMAL SKIN AS A BIOLOGICALLY RELEVANT EXPOSURE MEASUREMENT

Many human skin tumors contain mutated p53 genes that probably result from UV exposure. To investigate the link between UV exposure and p53 gene mutation, we developed two methods to detect presumptive UV-speci fic p53 gene mutations in UV-exposed normal skin. The methods are base d on mutant allele-specific PCRs and ligase chain reactions and design ed to detect CC to TT mutations at codons 245 and 247/248, using 10 mu g of DNA samples. These specific mutations in the p53 gene have been r eported in skin tumors. CC to TT mutations in the p53 gene were detect ed in cultured human skin cells only after UV irradiation, and the mut ation frequency increased with increasing UV dose. Seventeen of 23 sam ples of normal skin from sun-exposed sites (74%) on Australian skin ca ncer patients contained CC to TT mutations in one or both of codons 24 5 and 247/248 of the p53 gene, and only 1 of 20 samples from non-sun-e xposed sites (5%) harbored the mutation. None of 15 biopsies of normal skin from non-sun-exposed or intermittently exposed sites on voluntee rs living in France carried such mutations. Our results suggest that s pecific p53 gene mutations associated with human skin cancer are induc ed in normal skin by solar UV radiation. Measurement of these mutation s may be useful as a biologically relevant measure of UV exposure in h umans and as a possible predictor of risk for skin cancer.