Ellis E M, Judah D J, Neal G E, O'Connor T, Hayes J D
Biomedical Research Centre, Ninewells Hospital, Dundee, Scotland.
Cancer Res. 1996 Jun 15;56(12):2758-66.
Feeding rats on diets containing the synthetic antioxidants ethoxyquin, butylated hydroxyanisole, and oltipraz results in 15-, 9-, and 6-fold increases, respectively, in the hepatic levels of aflatoxin B1-dialdehyde reductase (AFAR) protein. By contrast, treatment of rats with either of the inducing agents phenobarbital or 3-methylcholanthrene results in an approximate increase of only 1.4-fold in the amount of AFAR in rat liver. Northern blotting has shown that these increases in levels of hepatic AFAR protein are accompanied by corresponding increases in AFAR mRNA. Immunodepletion of AFAR from rat liver extracts has revealed that AFAR makes a considerable contribution to carbonyl metabolism in livers from animals treated with synthetic antioxidants and that it is the major reductase that can utilize aflatoxin B1-dialdehyde as a substrate. The immunodepletion experiments also revealed the presence of at least one other inducible carbonyl-reducing enzyme that, like AFAR, can metabolize 9,10-phenanthraquinone. Carbonyl-reducing activity from rat liver has been resolved into six enzyme-containing peaks by anion-exchange chromatography on Q-Sepharose. This method has been used to show that, in addition to AFAR, two other rat liver carbonyl-reducing enzymes are induced by ethoxyquin, and that these are distinct from NAD(P)H: quinone oxidoreductase. Collectively, these data show that synthetic antioxidants can influence substantially the capacity of rat liver to metabolize reactive carbonyl-containing compounds.
用含有合成抗氧化剂乙氧喹、丁基羟基茴香醚和奥替普拉的饲料喂养大鼠，会使黄曲霉毒素B1 - 二醛还原酶（AFAR）蛋白的肝脏水平分别增加15倍、9倍和6倍。相比之下，用诱导剂苯巴比妥或3 - 甲基胆蒽处理大鼠，只会使大鼠肝脏中AFAR的量增加约1.4倍。Northern印迹法表明，肝脏中AFAR蛋白水平的这些增加伴随着AFAR mRNA的相应增加。从大鼠肝脏提取物中免疫去除AFAR表明，AFAR对用合成抗氧化剂处理的动物肝脏中的羰基代谢有相当大的贡献，并且它是能够利用黄曲霉毒素B1 - 二醛作为底物的主要还原酶。免疫去除实验还揭示了至少存在一种其他可诱导的羰基还原酶，它与AFAR一样，能够代谢9,10 - 菲醌。通过在Q - Sepharose上进行阴离子交换色谱，大鼠肝脏中的羰基还原活性已被分离为六个含酶峰。该方法已被用于表明，除了AFAR之外，另外两种大鼠肝脏羰基还原酶也被乙氧喹诱导，并且它们与NAD(P)H：醌氧化还原酶不同。总体而言，这些数据表明合成抗氧化剂可显著影响大鼠肝脏代谢含活性羰基化合物的能力。
