Infrequent p53 mutations in arsenic-related skin lesions.
Oral arsenic exposure increases the risk for a variety of benign and malignant skin lesions, but the molecular mechanism of the carcinogenic effect is poorly understood. Arsenic-related squamous cell carcinomas of the skin can 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 are frequent in nonmelanoma skin cancers, we studied p53 in 23 premalignant or malignant skin lesions from seven patients with a history of arsenic medication. The eighth patient studied (with six lesions) had a long standing exposure to UV radiation. Accumulation of the p53 protein was detected (with 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 repeatedly positive when p53 exons 5 to 8 were screened by a nonradioactive single-strand conformation polymorphism (SSCP) analysis. Only one of the arsenic-related lesions was confirmed by sequencing to have a mutation (a CC to TT double transition). No indications of mutations were found among the 18 basal cell carcinoma or two squamous cell carcinoma lesions studied. Our results 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 in the development of arsenic-induced skin cancers.
Castrén
K
K
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Ranki
A
A
Welsh
J A
JA
Vähäkangas
K H
KH
D000368:Aged; D000369:Aged, 80 and over; D001151:Arsenic / Q000009:adverse effects*; D002277:Carcinoma / Q000139:chemically induced / Q000235:genetics*; D002280:Basal Cell Carcinoma / Q000139:chemically induced / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics; D006801:Humans; D007642:Keratosis / Q000235:genetics; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012867:Skin / Q000528:radiation effects; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays
D016159:Tumor Suppressor Protein p53; D001151:Arsenic