Infrequent p53 mutations in arsenic-related skin lesions

Oral arsenic exposure increases the risk for a variety of benign and malign ant skin lesions, but the molecular mechanism of the carcinogenic effect is poorly understood. Arsenic-related squamous cell carcinomas of the skin ca n develop either de novo or progress from Bowen's disease lesions. Arsenic- related basal cell carcinomas develop usually in non-sun-exposed areas and are multiple. Because p53 tumor suppressor protein is a protective cellular molecule against environmental carcinogens and mutations in the p53 gene a re frequent in nonmelanoma skin cancers, we studied p53 in 23 premalignant or malignant skin lesions from seven patients with a history of arsenic med ication. The eighth patient studied (with six lesions) had a long-standing exposure to UV radiation. Accumulation of the p53 protein was detected (wit h a monoclonal DO-7 antibody) in 78% of the lesions from cases with arsenic exposure. Two of the six (30%) arsenic-related premalignant lesions and in addition one UV-related carcinoma in situ lesion were clearly and repeated ly positive when p53 exons 5 to 8 were screened by a nonradioactive single- strand conformation polymorphism (SSCP) analysis. Only one of the arsenic-r elated lesions was confirmed by sequencing to have a mutation (a CC to TT d ouble transition). Na indications of mutations were found among the 18 basa l cell carcinoma or two squamous cell carcinoma lesions studied. Our result s suggest that the frequent accumulation of p53 protein in arsenic-related skin lesions is not due to p53 mutations, which may not be a prerequisite i n the development of arsenic induced skin cancers.