火鸡肝微粒体对黄曲霉毒素 B1 的生物活化：起作用的细胞色素 P450 酶。

Bioactivation of aflatoxin B1 by turkey liver microsomes: responsible cytochrome P450 enzymes.

Laboratorio de Toxicologia, Facultad de Medicina Veterinaria y de Zootecnia, Universidad Nacional de Colombia, Bogota, D.C. Colombia.

Br Poult Sci. 2010 Dec;51(6):828-37. doi: 10.1080/00071668.2010.528752.

Abstract

A study was conducted to determine the cytochrome P450 enzymes responsible for the bioactivation of aflatoxin B1 into its epoxide form (AFBO) in turkey liver microsomes. 2. The strategies used included the measurement of prototype substrate activity for specific human P450s, use of selective inhibitors, determination of correlation between aflatoxin bioactivation and enzymatic activity of prototype substrates and the determination of immunoreactive proteins using antibodies against human P450s. 3. Enzymatic activity and immunoreactive proteins corresponding to the turkey orthologs CYP1A1, CYP1A2, CYP2A6 and CYP3A4 were detected, but not for the CYP2D6 ortholog. 4. The results of the inhibition and correlation studies strongly suggest that the turkey CYP2A6 ortholog and, to a lesser extent, the CYP1A1 ortholog, are involved in the bioactivation of aflatoxin B1 in turkey liver microsomes. 5. This is the first study reporting the role of CYP2A6 in the bioactivation of AFB1 in an avian species and the role of CYP1A1 in any species.

摘要

一项研究旨在确定细胞色素 P450 酶在火鸡肝微粒体中将黄曲霉毒素 B1 生物转化为环氧化物形式（AFBO）的作用。
所采用的策略包括测量特定人 P450 的原型底物活性、使用选择性抑制剂、确定黄曲霉毒素生物转化与原型底物酶活性之间的相关性以及使用针对人 P450 的抗体测定免疫反应性蛋白。
检测到对应于火鸡同源物 CYP1A1、CYP1A2、CYP2A6 和 CYP3A4 的酶活性和免疫反应性蛋白，但未检测到 CYP2D6 同源物。
抑制和相关性研究的结果强烈表明，火鸡 CYP2A6 同源物，并且在较小程度上，CYP1A1 同源物，参与了黄曲霉毒素 B1 在火鸡肝微粒体中的生物转化。
这是首次报道 CYP2A6 在禽类物种中 AFB1 生物活化中的作用以及 CYP1A1 在任何物种中的作用的研究。