Bogdanffy M S, Roberts A E, Schatz R A, Brown D R
Toxicol Lett. 1986 Apr;31(1):57-64. doi: 10.1016/0378-4274(86)90194-3.
Corticosterone was investigated for its ability to inhibit benzo(a)pyrene (BaP) metabolism and was compared to metyrapone and alpha-naphthoflavone. Corticosterone inhibited aryl hydrocarbon hydroxylase (AHH) activity nonlinearly in hepatic microsomes from uninduced, phenobarbital-induced, or 3-methylcholanthrene-induced rats. When compared to the classic inhibitors metyrapone and alpha-naphthoflavone, corticosterone had inhibitory properties similar to each. Metabolism of BaP to dihydrodiols was inhibited at the K-region by corticosterone only in uninduced microsomes. Dihydrodiol formation at the Bay region, which leads to the putative ultimate carcinogen, was not affected by corticosterone in uninduced or phenobarbital-induced microsomes but stimulated in 3-methylcholanthrene-induced microsomes. These findings suggest that corticosterone regioselectively inhibits cytochrome P-450 mediated oxidation of BaP to less mutagenic metabolites while stimulating the formation of highly mutagenic products.
研究了皮质酮抑制苯并(a)芘（BaP）代谢的能力，并将其与甲吡酮和α-萘黄酮进行了比较。皮质酮对未诱导、苯巴比妥诱导或3-甲基胆蒽诱导的大鼠肝微粒体中的芳烃羟化酶（AHH）活性具有非线性抑制作用。与经典抑制剂甲吡酮和α-萘黄酮相比，皮质酮具有相似的抑制特性。仅在未诱导的微粒体中，皮质酮在K区域抑制了BaP向二氢二醇的代谢。在未诱导或苯巴比妥诱导的微粒体中，导致推定最终致癌物的海湾区域二氢二醇的形成不受皮质酮影响，但在3-甲基胆蒽诱导的微粒体中受到刺激。这些发现表明，皮质酮区域选择性地抑制细胞色素P-450介导的BaP氧化为致突变性较低的代谢产物，同时刺激高致突变性产物的形成。
