DNA, SUNLIGHT AND SKIN-CANCER

Mutations in the p53 tumor suppressor genes in the most common types of skin cancer occur almost exclusively at dipyrimidine sites and are highly characteristic of UVB light. The UVB in sunlight produces cis-syn dimers and (6-4) products at dipyrimidine sites, the latter of which are isomerized by UVA/B light to their Dewar valence isomers. Which of these photoproduct classes is primarily responsible for the mutagenic and carcinogenic effects of sunlight is unknown and to approach this problem we have been developing methods for the construction and study of DNA containing unique photoproducts. Our studies have led us to a new proposal for the origin of C --> T mutations, the principal mutations induced by UVB light in many living systems and the major mutation found in the human p53 gene.