六氯苯致大鼠肝细胞色素P-450的性质。

G H Blekkenhorst, L Eales, N R Pimstone
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引用次数: 5

摘要

1. 研究了不同时间间隔饲粮中添加0.2% (w/w)六氯苯对雌性Wistar大鼠肝、尿卟啉和肝细胞色素P-450的影响。2. 六氯苯给药45天导致大鼠出现卟啉症,其生化性质与人类症状性卟啉症非常相似,尿尿卟啉排泄量、肝尿卟啉含量和肝细胞色素P-450含量升高,粪便中出现异比例卟啉(P1)系列卟啉。3.用一氧化碳和异氰酸乙酯作为配体,对45天诱导的肝细胞色素P-450的光谱研究表明,存在一种不同于细胞色素P-450的血红蛋白的混合物。4. 对肝微粒体细胞色素P-450依赖酶系统催化的氨基吡啶n -去甲基化和3,4-苯并芘羟基化两个反应的体外动力学研究表明,六氯苯诱导了一种细胞色素P-450依赖酶系统,六氯苯诱导的细胞色素P-450具有不同于苯巴比多或3-甲基胆蒽诱导的催化性质。
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The nature of hepatic cytochrone P-450 induced in hexachlorobenzene-fed rats.

1. The effect of feeding with a diet containing 0.2% (w/w) hexachlorobenzene on hepatic and urinary porphyrins and hepatic cytochrome P-450 was studied at various time intervals in female Wistar rats. 2. Hexachlorobenzene administration for 45 days resulted in the development of porphyria in rats, which biochemically closely resembles symptomatic porphyria in humans, with elevation of urinary uroporphyrin excretion, hepatic uroporphyrin content, and hepatic cytochrome P-450 content, in addition to appearance of porphyrins of the isocoproporphyrin (P1) series in the faeces. 3. Spectral studies of the induced hepatic cytochrone P-450 at 45 days with carbon monoxide and ethyl isocyanide as ligands indicated the presence of a greater admixture of a haemoprotein distinct from cytochrome P-450. 4. Study in vitro of the kinetics of two reactions, namely aminopyrine N-demethylation and 3,4-benzpyrene hydroxylation, catalysed by the hepatic microsomal cytochrom P-450-dependent enzyme system, suggested that hexachlorobenzene induced a form of cytochrome P-450-dependent enzyme system, suggested that hexachlorobenzene induced a form of cytochrome P-450 with different catalytic properties from those of forms induced by either phenobarbital or 3-methylcholanthrene.

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