来自经3-甲基胆蒽预处理大鼠的纯化肝细胞色素P-450对致癌物2-乙酰氨基芴的氧化激活和失活的抗体抑制作用。

Antibody inhibition of oxidative activation and inactivation of the carcinogen 2-acetylaminofluorene by purified hepatic cytochrome P-450 from 3-methylcholanthrene pretreated rats.

作者信息

Pandey R N, Clearfield M S, Paik S M, Lotlikar P D

出版信息

Cancer Lett. 1983 Jul;19(3):263-71. doi: 10.1016/0304-3835(83)90094-0.

Abstract

Immunochemical studies on metabolic N- and ring hydroxylation of 2-acetylaminofluorene (AAF) were performed with total cytochrome P-450 isozymes and with highly purified P-450 D isozyme isolated from liver microsomes from 3-methylcholanthrene (MC)-pretreated rats. In a reconstituted system with rat P-450 D, addition of antibodies against beta-naphthoflavone (BNF) induced rat P-450 B at 15 mg IgG/nmol P-450 inhibited both oxidations completely. With total P-450 isozymes in a reconstituted system, antibody against BNF-rat-P-450 B at 20 mg IgG/nmol P-450 inhibited both oxidations up to 70-80% only. At these concentrations, preimmune antibody or phenobarbital (PB) induced antibody against rat-P-450 B showed no inhibition of AAF oxidations. These results suggest that P-450 D is the predominant cytochrome P-450 isozyme responsible for AAF N- and ring-oxidations in liver microsomes from MC-pretreated rats. Other P-450 isozymes are also suggested to be involved in AAF oxidations.

摘要

利用总细胞色素P-450同工酶以及从经3-甲基胆蒽（MC）预处理的大鼠肝脏微粒体中分离得到的高度纯化的P-450 D同工酶，对2-乙酰氨基芴（AAF）的代谢性N-羟基化和环羟基化进行了免疫化学研究。在含有大鼠P-450 D的重组系统中，加入抗β-萘黄酮（BNF）抗体，当IgG浓度为15 mg/nmol P-450时诱导产生大鼠P-450 B，此时两种氧化反应均被完全抑制。在重组系统中使用总P-450同工酶时，当IgG浓度为20 mg/nmol P-450的抗BNF-大鼠-P-450 B抗体仅能将两种氧化反应抑制70 - 80%。在这些浓度下，免疫前抗体或苯巴比妥（PB）诱导产生的抗大鼠-P-450 B抗体对AAF氧化反应无抑制作用。这些结果表明，P-450 D是负责经MC预处理的大鼠肝脏微粒体中AAF N-羟基化和环氧化反应的主要细胞色素P-450同工酶。也有证据表明其他P-450同工酶参与了AAF的氧化反应。