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

环境中内分泌干扰物风险评估与澄清。

• 批准号: 11358009
• 负责人: FUJITA Shoichi
• 金额: $ 22.64万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11358009/
• 关键词: biomarker; endocrine disrupting chemicals; CYP1A; Cytochrome P450; wild life; steroid hormone; environmental pollution; dioxin; 環境ホルモン; 環境汚染; ステロイドホルモン; ダイオキシン受容体; PPAR; Ah受容体; ベンゾピレン; フタル酸エステル; ビスフェノールA; ゴマフアザラシ; クラカケアザラシ; オオワシ; オジロワシ

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.

为探讨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价工具的有效性，测定了日本北海道沿岸沃茨的大海豹和斑海豹鲸脂中的氯代烃（CHC）含量，以评价CHC暴露对动物激素的影响。在这些动物中，CYP1A表达水平与CHC蓄积水平一致。我们还试图分离P450亚型，如CYP1A和CYP3A亚家族，它们有助于消除哺乳动物体内的异生素和类固醇激素。本研究测定了CYP1A1、CYP1A2和CYP3A的序列和酶学性质，并研究了CHC对鱼类外源性物质代谢和激素稳态的影响。我们收集了雄鱼和雌鱼，从Hikiji河，在那里含有二恶英的未经处理的污水已经被释放到河水中七年半。CYP1A亚家族的表达水平与二恶英积累水平相一致。相反，雌激素水平和性腺指数（GSI）值降低，从二恶英污染的河流收集的雌鱼。

项目成果

佐治尚介, 坂本健太郎, 石塚真由美, 数坂昭夫, 藤田正一: "ウグイを用いた小樽、石狩、美国港周辺の環境汚染の評価"野生生物と交通. 2. 37-44 (2002)

Naosuke Saji、Kentaro Sakamoto、Mayumi Ishizuka、Akio Kazusaka、Shoichi Fujita：“利用日本鲮鱼评估小樽、石狩和三国港口周围的环境污染”野生动物和运输。

Maruyama Y, et al.: "Norsalsolinol uptake into secretory vesicles via vesicular monoamine transporter and its secretion by membrane depolarization or purinoceptor stimulation in PC12 cells"J Vet Med Sci. 63. 493-497 (2001)

Maruyama Y 等人：“Norsalsolinol 通过囊泡单胺转运蛋白摄取到分泌囊泡中，并通过 PC12 细胞中的膜去极化或嘌呤受体刺激进行分泌”J Vet Med Sci。

Ishizuka M, Yamamoto Y, Takada A, Kazuska A, Fujita S.: "The loss of enzyme activities by a single amino acid substitution of a newly cloned rabbit CYP2D isozyme, CYP2D24. International congress series 1233"Elsvier. 545(121-126) (2002)

Ishizuka M、Yamamoto Y、Takada A、Kazuska A、Fujita S.：“新克隆的兔 CYP2D 同工酶 CYP2D24 的单个氨基酸取代导致酶活性丧失。国际大会系列 1233”Elsvier。

Nakamura, A., Hirota, T., Morino, A., Imaoka, S., Funae, Y., Yamamoto, Y., Tasaki, T., Masuda, M., Kazusaka, A., Fujita, S.: "Cytochrome P450 isoforms responsible for the N-deethylation and cyclohexane-hydroxylation of NS-21"Xenobiotica. 29,No.3. 243-252

Nakamura, A.、Hirota, T.、Morino, A.、Imaoka, S.、Funae, Y.、Yamamoto, Y.、Tasaki, T.、Masuda, M.、Kazusaka, A.、Fujita, S.：

Shimamoto, Y., Tasaki T, Kitamura, H., Hirose K, Kazusaka A, Fujita S.: "Decrease in hepatic CYP2C11 mRNA and increase in heme oxygenase activity after intracerebroventricular injection of bacterial endotoxin"J Vet Med Sci.. Jun;61(6). 609-613 (1999)

Shimamoto, Y.、Tasaki T、Kitamura, H.、Hirose K、Kazusaka A、Fujita S.：“脑室内注射细菌内毒素后，肝脏 CYP2C11 mRNA 减少，血红素加氧酶活性增加”J Vet Med Sci. Jun；