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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental pollutant which has been shown to be both a potent teratogen and carcinogen and also to have tumor-promoting activity. We have compared TCDD with the proto-type phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) using the metabolic cooperation assay as a measure of tumor promotional competence. Unlike TPA, TCDD was found to be ineffective in inhibiting metabolic cooperation at concentrations which elicit many of TCDD's biological responses. These results suggest that TPA and TCDD elicit tumor promotion by different pathways. We discuss these results in the context of cell-type-specific and TCDD receptor-mediated biological responses to tumor promoters.

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