Bacher M A, Gibson G G
Department of Biochemistry, University of Surrey, Guildford, U.K.
Chem Biol Interact. 1988;65(2):145-56. doi: 10.1016/0009-2797(88)90051-8.
Induction of the cytochrome P-450 mixed-function oxidase and specifically the cytochrome P-450 IVA1 isoenzyme by seven phenoxyacid herbicides in rat liver have been studied. Liver microsomes from rats orally treated with the herbicides at 3 dose levels showed a significant increase in total cytochrome P-450 content with 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) being the most potent inducer. Benzphetamine N-demethylation, as a marker of cytochrome P-450b (P-450 IIB1) activity, was not affected by any of the herbicides studied, whereas cytochrome P-450c (P-450 IA1), as assayed by ethoxyresorufin-O-deethylation activity, was significantly increased (up to 2.2-fold) by some of the herbicides. The 12-hydroxylation of lauric acid was significantly induced (3-8-fold) by all seven herbicides, 4-chlorophenoxyacetic acid (CPA) and 2,4,5-trichlorophenoxypropionic acid (2,4,5-TP) being the weakest and most potent inducers respectively. This increase in lauric acid 12-hydroxylase activity was accompanied by an increase in the hepatic content of cytochrome P-450 IVA1 as assessed by both a qualitative Western blot procedure and a quantitative ELISA method. By comparison, lauric acid 11-hydroxylase activity was not or only marginally increased by phenoxyacid herbicide pretreatment. Our results suggest that the phenoxyacid herbicides act as mixed inducers of the cytochrome P-450 mixed function oxidase system, preferentially inducing the cytochrome P-450 IVA1 isoenzyme.
研究了七种苯氧羧酸类除草剂对大鼠肝脏细胞色素P - 450混合功能氧化酶，特别是细胞色素P - 450 IVA1同工酶的诱导作用。用三种剂量水平的除草剂经口处理大鼠后获得的肝脏微粒体显示，细胞色素P - 450的总含量显著增加，其中2,4,5 - 三氯苯氧乙酸（2,4,5 - T）是最有效的诱导剂。作为细胞色素P - 450b（P - 450 IIB1）活性标志物的苄非他明N - 脱甲基作用，不受所研究的任何一种除草剂的影响，而通过乙氧苯腙 - O - 脱乙基活性测定的细胞色素P - 450c（P - 450 IA1），则被某些除草剂显著诱导（高达2.2倍）。所有七种除草剂均显著诱导月桂酸的12 - 羟化作用（3 - 8倍），其中4 - 氯苯氧乙酸（CPA）和2,4,5 - 三氯苯氧丙酸（2,4,5 - TP）分别是最弱和最强的诱导剂。通过定性蛋白质免疫印迹法和定量酶联免疫吸附测定法评估，月桂酸12 - 羟化酶活性的这种增加伴随着细胞色素P - 450 IVA1肝脏含量的增加。相比之下，苯氧羧酸类除草剂预处理对月桂酸11 - 羟化酶活性没有影响或仅有轻微增加。我们的结果表明，苯氧羧酸类除草剂作为细胞色素P - 450混合功能氧化酶系统的混合诱导剂，优先诱导细胞色素P - 450 IVA1同工酶。
