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Correlation between sensitivity to tumor promotion and sustained epidermal hyperplasia of mice and rats treated with 12-O-tetradecanoylphorbol-13-acetate
Environmental Carcinogenesis Group, Laboratory of Pulmonary Function and Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park, NC 27709, USA.
1To whom requests for reprints should be addressed.
The role of sustained hyperplasia in tumor promotion has been reexamined in light of our previous report that the Syrian hamster, which is insensitive to two-stage epidermal carcinogenesis initiated by DMBA and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA), does not respond with epidermal hyperplasia after multiple treatments with the promoter. Epidermal hyperplasia of several other species and strains of animals, which vary in their responsiveness to TPA-mediated tumor promotion, was examined after single or multiple treatments with the tumor promoter TPA. It was found that CD-1 mice, a strain which is responsive to TPA-induced tumor promotion, reacted with a slight degree of hyperplasia after a single exposure to the chemical and this response was potentiated after several treatments. C57B1 mice, a strain marginally responsive to TPA promotion, displayed only slight hyperplasia after single and multiple treatments. Ba1b/c mice, which are intermediately responsive to TPA-mediated promotion, displayed considerable epidermal hyperplasia after a single dose of TPA which was maintained after multiple treatments but at a reduced level. DBA mice, only marginally responsive to TPA promotion, showed considerable hyperplasia after a single dose of TPA which was maintained after multiple treatments but at a reduced level. DBA mice, only marginally responsive to TPA promotion, showed considerable hyperplaisa which was potentiated by multiple treatments. F344 rats, which are relatively insensitive to TPA promotion, showed a moderate hyperplastic response after a single dose which was reduced slightly after multiple treatments. A striking difference was observed in the response of the different animal species to single versus multiple exposures to the promoter. When the effects of single versus multiple doses of TPA were compared, every possible combination of responses was observed, including potentiation, adaptation, and no change. Thus, the results of a single exposure could not be used to predict the response with multiple treatments. While no correlation was observed between sensitivity to tumor promotion and hyperplasia induced by a single exposure of TPA, a good correspondence was found between sensitivity to tumor promotion and TPA induced sustained hyperplasia after 4 weeks of treatment. The role of sustained hyperplasia in tumor promotion and the necessity to study persistent effects induced by TPA are discussed.
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