Metabolic activation of endocrine-disruptors in animal body

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The metabolic activation of endocrine disrupters was examined in this study.1. Estrogenic activity was estimated by the reporter assay using human breast cancer cell line MCF-7. We found some proestrogens which were not estrogenic and produced their activities after the incubation with liver microsomes in the presence of NADPH. As proestrogens, we detected 2-nitrofluorene, trans-stilbene, biphenyl, diphenylmethane, dibenzyl, 2, 2-diphenylpropane, benzylideneacetone, styrene oligomers, diphenylamine, diphenylsulfone, azobenzene, pyrene, permethrin, dimethylphthalate and chalchone by screening the estrogenic activities of their metabolites. These proestrogens were converted to their hydroxylated active metabolites in vivo and in vitro in rats. The hydroxylation was mediated by liver microsomal cytochrome P450 2B1 or 1A1. 2. Bisphenol A, fluorene, pyrene, DDTs and some organophosphorus insecticides exhibited antiandrogenic activity. Fenthion sulfoxide also exhibited the activity after incubation with rat liver preparations. 3. Tetrabromobisphenol A, a flame retardant, exhibited thyroid hormonal activity. Some PCBs also exhibited the activity after the hydroxylation by cytochrome P450 system. 4. Trans-Stilbene, 2-nitrofluorene and fenthion showed endocrine-disrupting actions in vivo in rats. 5. When male goldfish were kept in the water containing trans-stilbene, diphenyl or 2-nitrofluorene (5x10^<-6> M) for five days, the vitellogenin level in blood was markedly increased. These hydroxylated compounds were detected in keeping water. These facts suggest that these proestrogens were activated to estrogens in mammals and fish.