Chlorpromazine reduces UV-induced squamous cell carcinogenesis in hairless mice and enhances UV-induced DNA damage in cultured cells.
Administration of the photoactivable compound chlorpromazine (CPZ) to SKH-1 hairless mice via their drinking water (CPZ, 0.01%) significantly reduced the rates of accumulation and yields of squamous cell carcinomas induced by long-term repeated exposures of these animals to solar UV radiation. This protective effect of CPZ was partially reversed in mice given a single injection of ethyl nitrosourea at birth. In in vitro studies, the presence of CPZ (0.2 mM) in mammalian cell cultures enhanced the yield of DNA single-strand breaks induced in the cells by exposure to monochromatic UVA radiation at 334 nm. Collectively, the results suggest that CPZ may exert antineoplastic effects against UV-induced skin tumours by the induction of DNA damage.
Biological, Environmental, and Medical Research Division, Argonne National Laboratory, IL 60439-4833.
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MJ
Peak
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Pfaff
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Peraino
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000517:prevention & control*; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000528:radiation effects*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control; D014466:Ultraviolet Rays / Q000009:adverse effects*
D004273:DNA, Neoplasm; D002746:Chlorpromazine