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2,4,5,2',4',5'-六溴联苯的光解产物:对Sprague-Dawley大鼠肝微粒体酶的诱导作用及毒性

Photolysis products of 2,4,5,2',4',5'-hexabromobiphenyl: hepatic microsomal enzyme induction and toxicity in Sprague-Dawley rats.

作者信息

Millis C D, Mills R, Sleight S D, Aust S D

出版信息

Fundam Appl Toxicol. 1985 Jun;5(3):555-67. doi: 10.1016/0272-0590(85)90103-4.

DOI:10.1016/0272-0590(85)90103-4
PMID:2989055
Abstract

The irradiation of 2,4,5,2',4',5'-hexabromobiphenyl (2,4,5-HBB) by ultraviolet light created a mixture of lower brominated polybrominated biphenyl (PBB) congeners. Three photoproducts, 2,4,5,3',4'-pentabromobiphenyl (-PBB), 2,4,5,2',5'-PBB, and 3,4,3',4'-tetrabromobiphenyl (3,4-TBB), as well as 2,4,5-HBB and the photolyzed 2,4,5-HBB mixture, were administered to rats as a single ip injection (90 mg/kg, except 3,4-TBB, which was given at 2 mg/kg) 2 weeks before sacrifice. All treatments except 3,4-TBB induced NADPH-cytochrome P-450 reductase and aminopyrine-N-demethylase activities while all treatments except 2,4,5-HBB induced ethoxyresorufin-O-deethylase and UDP-glucuronosyltransferase activities. Thymus to body weight and spleen to body weight ratios were unchanged compared to controls for all treatments whereas an increase in the liver weights was observed for all treatment groups. Histologic examination revealed that the photolyzed 2,4,5-HBB mixture caused moderate to severe hepatocyte enlargement. Results of tissue analysis for the pure PBB congeners indicated that 2,4,5,2',5'-PBB and 3,4-TBB were metabolized in vivo and this was confirmed by in vitro metabolism studies. The results revealed that the photolyzed 2,4,5-HBB mixture caused a mixed-type induction of hepatic drug-metabolizing enzymes. This is most likely due to the effect of 2,4,5-HBB and toxic congeners formed during the irradiation of 2,4,5-HBB. 2,4,5,3',4'-PBB, which is toxic and apparently not metabolized, is believed to be the major congener contributing to the increased toxicity of the photolyzed 2,4,5-HBB mixture since 3,4-TBB was metabolized and appeared not to be as potent as inducer of aryl hydrocarbon hydroxylase activity.

摘要

用紫外光照射2,4,5,2',4',5'-六溴联苯(2,4,5-HBB)会产生低溴化多溴联苯(PBB)同系物的混合物。三种光产物,即2,4,5,3',4'-五溴联苯(-PBB)、2,4,5,2',5'-PBB和3,4,3',4'-四溴联苯(3,4-TBB),以及2,4,5-HBB和光解的2,4,5-HBB混合物,在处死大鼠前2周以单次腹腔注射的方式给予大鼠(90毫克/千克,但3,4-TBB给予剂量为2毫克/千克)。除3,4-TBB外的所有处理均诱导了NADPH-细胞色素P-450还原酶和氨基比林-N-脱甲基酶活性,而除2,4,5-HBB外的所有处理均诱导了乙氧基异吩恶唑酮-O-脱乙基酶和UDP-葡萄糖醛酸基转移酶活性。与对照组相比,所有处理组的胸腺与体重比和脾脏与体重比均未改变,而所有处理组的肝脏重量均增加。组织学检查显示,光解的2,4,5-HBB混合物导致中度至重度肝细胞肿大。对纯PBB同系物的组织分析结果表明,2,4,5,2',5'-PBB和3,4-TBB在体内被代谢,体外代谢研究证实了这一点。结果显示,光解的2,4,5-HBB混合物引起肝脏药物代谢酶的混合型诱导。这很可能是由于2,4,5-HBB以及2,4,5-HBB照射过程中形成的有毒同系物的作用。2,4,5,3',4'-PBB有毒且显然未被代谢,被认为是导致光解的2,4,5-HBB混合物毒性增加的主要同系物,因为3,4-TBB被代谢且似乎作为芳烃羟化酶活性诱导剂的效力不如前者。

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