OHTA Shigeru Hiroshima University Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (60160503)
WATANABE Hiromitsu Hiroshima University Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (00034653)
FUJIMOTO Nariaki Hiroshima University Research Institute for Radiation Biology and Medicine, Associate Professor, 原爆放射線医科学研究所, 助教授 (40243612)
SUGIHARA Kazumi Hiroshima University, Faculty of Medicine, Teaching Associate, 医学部, 教務員 (20271067)
|Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥2,900,000 (Direct Cost: ¥2,900,000)
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.