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Minimal role of enhanced cell proliferation in skin tumor promotion by mirex: a nonphorbol ester-type promoter.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Moser, Glenda J. Monteiro-Riviere, Nancy A. |
| Copyright Year | 1993 |
| Abstract | 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. |
| Starting Page | 265 |
| Ending Page | 269 |
| Page Count | 5 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 8013418 |
| Volume Number | 101 |
| Journal | Environmental health perspectives |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Carboxy-Lyases Cell Proliferation DNA Replication Epidermis Esters Flame Retardants Hydrocarbons Hydrocarbons, Chlorinated Hyperplasia Liver neoplasms Mirex NG-Nitroarginine Methyl Ester Nucleated cell Ornithine Decarboxylase Promotion (action) Skin Neoplasms Tetradecanoylphorbol Acetate Tumor Promoters Tumor Promotion anatomical layer multiplicity negative regulation of sinapate ester biosynthetic process |
| Content Type | Text |
| Resource Type | Article |
