Metabolism of polychlorinated and polybrominated pollutants in mammals and human health

哺乳动物中多氯和多溴污染物的代谢与人类健康

• 批准号: 12672180
• 负责人: HARAGUCHI Koichi
• 金额: $ 2.05万
• 依托单位: Daiichi College of Pharmaceutical Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672180/
• 关键词: PCB; methylsulfonyl metabolites; hydroxylated metabolites; tissue distribution; whales; human; species difference; thyroid hormone; メチルスホルン代謝物; 有機臭素化合物; 海棲哺乳動物; 体内動態; ポリ臭化ビフェニル

(1). Species difference in metabolism of PCBTissue distribution of hydroxylated and methylsulfonyl PCB were largely different among rats, mice, guinea pigs and hamsters after exposure to 2,4,5,2',5'-pentaCB (CB101) and 2,3,4,2',3',6'-hexaCB (CB132). Hamster blood strongly retained a catechol metabolite from CB132. Gunn rats, hereditarily UGT1s deficient, highly produced catechol metabolites derived from CB110 and CB149 after exposure to Kanechlor 500.(2). Metabolism of polybrominated biphenyl and enzyme induction3'-MeSO_2-2,4,2',5'-tetraBrB, a metabolite of 2,4,2',5'-tetraBrB, was found to be a potent inducer of CYP2B1/2 in rats. Unlike MeSO_2-PCBs, this metabolite showed no reduction of thyroid hormone (T4) level in rat serum.(3). Halogenated pollutants in whale meat and its biological effects.Several brominated compounds as well as chlorinated ones (PCB, DDTs and chlordanes) were detected in whale products. Exposure of mice to the organohalogen contaminants in blubber products resulted in changes of some biochemical parameters (GPT, amylase and T4) in serum. Also, these pollutants were exposed to cultured rat embryos during organogenesis, where the tetratogenicity was observed in a dose-dependent manner.(4). MeSO_2-PCBs in human liverHuman liver was analyzed for MeSO_2-PCBs by negative CI/GC/MS technique. A major component was 5'-MeSO_2-2,3,4,2',3',6'-hexaCB (about 60% of total MeSO_2-PCBs), followed by 3- or 4-MeSO_2 metabolites derived from CB87, CB101 and CB149.

(1)。多氯联苯代谢的物种差异2，4，5，2‘，5’-五氯苯(CB101)和2，3，4，2‘，3’，6‘-六氯苯(CB132)对大鼠、小鼠、豚鼠和仓鼠的羟化多氯联苯和甲磺酰基多氯联苯的分布有很大差异。仓鼠血中强烈保留CB132的儿茶酚代谢物。Gunn大鼠是遗传性UGT1缺乏的大鼠，暴露于卡内克洛500后，CB110和CB149产生大量儿茶酚代谢产物。多溴联苯的代谢和酶诱导2，4，2‘，5’-四溴联苯的代谢产物3‘-Meso_2-2，4，2’，5‘-四溴联苯对大鼠体内的细胞色素P450_2B1/2有很强的诱导作用。与Meso_2-PCbs不同，该代谢产物不降低大鼠血清甲状腺激素(T4)水平。鲸鱼肉中的卤代污染物及其生物效应。在鲸鱼产品中检测到几种溴化物和氯化化合物(多氯联苯、滴滴涕和氯丹)。小鼠暴露于脂肪制品中的有机卤素污染物后，血清中某些生化指标(谷丙转氨酶、淀粉酶和T4)发生了变化。此外，在器官发生过程中，这些污染物被暴露在培养的大鼠胚胎中，并以剂量依赖的方式观察到四致毒性。用负CI/GC/MS技术分析人肝组织中的Meso_2-PCbs。主要成分为5‘-Meso_2-2，3，4，2’，3‘，6’-六CB(约占Meso_2-PCCs总量的60%)，其次是CB87、CB101和CB149的3-或4-Meso_2代谢物。

项目成果

N.Koga: "Species differences in the in vitro metabolism of 2,4,5,2',3',4'-hexachlorobiphenyl"Fukuoka Acta Med.. 92. 167-176 (2001)

N.Koga：“2,4,5,2,3,4-六氯联苯体外代谢的物种差异”Fukuoka Acta Med.. 92. 167-176 (2001)

T.Endo: "Renal toxicity in rats after oral administration of mercury-contaminated boiled whale livers marketed for human consumption in Japan"Arch. Environ. Contam. Toxicol.. 44. 412-413 (2003)

T.Endo：“大鼠口服日本供人类食用的受汞污染的煮鲸肝后出现肾毒性”Arch.

Y. Kato: "Effects of polychlorinated biphenyls, Kanechlor-500, on serum thyroid hormone levels in rats and mice"Toxicol. Sci.. 72. 235-241 (2003)

Y. Kato：“多氯联苯 Kanelor-500 对大鼠和小鼠血清甲状腺激素水平的影响”Toxicol。

Y.Kato.: "Effects of polychlorinated biphenyls (Kanechlor-500) on serum hormone levels in rats and mice"Organohalogen Compounds. 53. 47-49 (2001)

Y.Kato.：“多氯联苯 (Kanelor-500) 对大鼠和小鼠血清激素水平的影响”有机卤素化合物。

Y.Kato: "Reduction of serum of thyroxine concentrations by methylsulfonyl metabolites of tetra-, penta-and hexachiorinated biphenyls in male Sprague-Dawley rats"Chemosphere. 40. 1233-1240 (2000)

Y.Kato：“雄性 Sprague-Dawley 大鼠中四、五和六氯代联苯的甲磺酰代谢物降低血清甲状腺素浓度”Chemosphere。