Promotion of skin carcinogenesis by dimethylarsinic acid in keratin (K6)/ODC transgenic mice

Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals in mammals, and arsenic exposure is associated with tumor development in a wi de variety of human tissues, particularly the skin. Transgenic mice with or nithine decarboxylase (ODC) targeted to hair follicle keratinocytes are muc h more sensitive than littermate controls to carcinogens. In this study we investigated the promoting effect of DR DMA on skin carcinogenesis in such K6/0DC transgenic mice. The back skin of female C57BL/6J k6/0DC transgenic mice, 10 to 14 weeks old, was initiated with topical application of 7,12-di methylbenz[a]anthracene (DMBA) at a dose of 50 mu g or acetone alone on day 1 of the experiment, followed by treatment with 3.6 mg of DMA, 5 mu g of 1 2-O-tetradecanoylphorbol-13-acetate (TPA) or neutral: vehicle (control) twi ce a week for 18 weeks. Mice were killed 1 week after the end of the treatm ent. Induction of skin tumors was significantly accelerated in the DMA-trea ted group, as well as in the TPA-treated group, indicating that DMA has a p romoting effect on skin tumorigenesis in K6/0DC transgenic mice.