The risk assessment and clarification of endocrine disrupting chemicals in environment. Use of P450 for the biomonitoring and bioremediation of environmental pollution-

为了研究P450作为环境内分泌干扰物对野生动物影响的生物标志物和评估工具的有效性，对采自日本北海道沿海水域的大海豹和带状海豹的鲸脂中氯代烃(CHC)水平进行了测定，以评估CHC暴露对激素的影响。在这些动物中，CYP1A的表达水平与CHC的积累水平一致。我们还试图分离出P450亚型，如CYP1A和CYP3A亚家族，它们有助于消除异物和促进哺乳动物类固醇激素的分解代谢。我们测定了细胞色素P1A1、细胞色素P1A2和细胞色素P3A的序列和酶学性质，并研究了CHC对鱼类异源代谢和激素稳态的影响。我们从Hikiji河收集了雄性和雌性鲤鱼，那里的含有二恶英的未经处理的污水已经排放到河水中七年半了。细胞色素P1A亚家族的表达水平与二恶英蓄积水平一致。相比之下，从二恶英污染的河流采集的雌性鲤鱼的雌激素水平和性腺躯体指数(GSI)值都降低了。

The usefulness of P450 as a biomarker and an assessing tool for the impact of environmental endocrine disrupting chemicals on the wild animals was studied.Chlorinated hydrocarbon (CHC) levels in the blubber of Larga seals and Ribbon seals collected from the coastal waters of Hokkaido, Japan were determined in order to assess the hormonal effects of CHC exposure. In these animals, CYP1A expression levels were coincided with CHC accumulation levels. We also tried to isolate P450 isoforms such as CYP1A and CYP3A subfamilies, which contributed to elimination of xenobiotic and to catabolism of steroid hormone in mammals. We detemined the sequences and enzymatic characters of CYP1A1, CYP1A2 and CYP3A forms.We also investigated the CHC effects on xenobiotic metabolisms and hormonal homeostasis in fish. We collected male and female carps from Hikiji river, where raw sewage containing dioxins had been released into river water for seven and a half years. The expression levels of CYP1A subfamily were coincided with dioxin accumulation levels. In contrast, estrogen level and GSI (gonadal somatic index) value were reduced in female carps collected from dioxin-contaminated river.