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[给予MC型异生物质后近交系小鼠肝脏微粒体中细胞色素P - 448的诱导作用]

[Cytochrome P-448 induction in liver microsomes of mice of inbred strains after administration of xenobiotics of MC-type].

作者信息

Mishina D V, Mishin V M, Liakhovich V V

出版信息

Biokhimiia. 1986 May;51(5):719-28.

PMID:3708017
Abstract

Using immunochemical methods, the identity of cytochrome P-448 from liver microsomes of mice of "inducible" and "non-inducible" lines during induction by xenobiotics of MX-type (3-methylcholanthrene, 3,4-benzpyrene, 2,3,7,8-tetrachlorodibenzodioxin) was established. This hemoprotein form was shown to play a role in 3,4-benzpyrene metabolism. Monospecific antibodies to purified cytochromes P-448 and P-450 were obtained; the cytochrome P-448 content in microsomes was measured by rocket immunoelectrophoresis. The content of cytochrome P-448 in control and phenobarbital-induced microsomes makes up to 10-15% of the total hemoprotein content determinable from the CO-spectra. 3-Methylcholanthrene and 3,4-benzpyrene injected into "non-inducible" mice cause no increase in the content of this hemprotein form, whereas in mice induced with 2,3,7,8-tetrachlorodibenzodioxin it rises to 50%. Under these conditions, an almost 100% inhibition of 3,4-benzpyrene metabolism by antibodies to cytochrome P-448 is observed. Antibodies against cytochrome P-448 obtained from liver microsomes of 3-methylcholanthrene-induced mice cause a 90% inhibition of 3,4-benzpyrene in microsomes induced with 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzodioxin.

摘要

采用免疫化学方法,确定了“可诱导”和“不可诱导”品系小鼠肝脏微粒体中细胞色素P - 448在MX型(3 - 甲基胆蒽、3,4 - 苯并芘、2,3,7,8 - 四氯二苯并二恶英)外源化合物诱导过程中的特性。这种血红蛋白形式在3,4 - 苯并芘代谢中发挥作用。获得了针对纯化的细胞色素P - 448和P - 450的单特异性抗体;通过火箭免疫电泳测定微粒体中细胞色素P - 448的含量。对照和苯巴比妥诱导的微粒体中细胞色素P - 448的含量占可通过一氧化碳光谱测定的总血红蛋白含量的10 - 15%。给“不可诱导”的小鼠注射3 - 甲基胆蒽和3,4 - 苯并芘不会导致这种血红蛋白形式的含量增加,而在用2,3,7,8 - 四氯二苯并二恶英诱导的小鼠中,其含量会升至50%。在这些条件下,观察到细胞色素P - 448抗体对3,4 - 苯并芘代谢有近100%的抑制作用。从3 - 甲基胆蒽诱导的小鼠肝脏微粒体中获得的抗细胞色素P - 448抗体对3 - 甲基胆蒽和2,3,7,8 - 四氯二苯并二恶英诱导的微粒体中的3,4 - 苯并芘有90%的抑制作用。

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