摘要：Mirex, a chlorinated hydrocarbon previously used as a systemic insecticide and flame retardant, is a nongenotoxic hepatocarcinogen in both rats and mice. In liver, mirex induced biochemical responses and hyperplasia characteristic of increased cell proliferation, which is consistent with its role as a liver tumor promoter. We have recently shown that mirex is a potent nonphorbol ester-type skin tumor promoter in 7, 12-dimethylbenz[a]anthracene (DMBA)-initiated mice. However, unlike its effect in liver, a single topical application of mirex to skin does not induce the acute biochemical responses, such as increased epidermal DNA synthesis and ornithine decarboxylase activity, indicative of increased cell proliferation. Multiple topical applications of mirex over a 1 month period induced only a minimal increase in the number of epidermal nucleated cell layers, which contrasts with definitive hyperplasia induced by a comparable tumor-promoting dose of 12-O-tetradecanoylphorbol-13-acetate (TPA). Collectively, these data indicated that mirex is promoting through a novel mechanism. Further evidence that mirex promotes tumors through a mechanism distinct from that of the prototypical skin tumor promoter, TPA, was obtained by examining the effect of their simultaneous co-treatment. The co-application of mirex and TPA yielded a tumor multiplicity greater than the sum of the responses of each promoter individually. In summary, our results demonstrate that mirex, a carcinogenic and hyperplastic agent in liver, is also a very effective tumor promoter in mouse skin, but suggest that mirex operates via a novel mechanism in skin that may involve only a minimal role for enhanced cell proliferation. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . 265 266 267 268 269
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