Nesnow S, Jackson L, Padgett W T, Lambert G R, Agarwal S C
Carcinogenesis and Metabolism Branch, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Cancer Lett. 1993 Sep 30;73(2-3):135-40. doi: 10.1016/0304-3835(93)90255-8.
The ability of reduced polycyclic aromatic hydrocarbons to be converted to their fully aromatic forms by the microsomal cytochrome P-450 mixed-function oxidases may assist in the explanation of the mutagenic and tumorigenic activities of these agents. The metabolic conversion of 9,10-dihydrobenzo[a]pyrene (9,10-DHB[a]P) to benzo[a]pyrene (B[a]P) and 9- and/or 10-hydroxy-9,10-DHB[a]P (OH-9,10-DHB[a]P) was quantitatively measured. In beta-naphthoflavone-induced rat liver microsomes, 9,10-DHB[a]P was metabolized to B[a]P with a specific activity of 1.51 nmol B[a]P formed/min/mg microsomal protein. The formation of B[a]P was directly related to incubation time and microsomal protein concentration. Similarly, 9,10-DHB[a]P was converted to OH-9,10-DHB[a]P with a specific activity of 4.48 nmol OH-9,10-DHB[a]P formed/min/mg microsomal protein. Its formation was directly related to incubation time and microsomal protein concentration. The possibility of OH-9,10-DHB[a]P as a metabolic intermediate to B[a]P is discussed.
还原态多环芳烃能够被微粒体细胞色素P - 450混合功能氧化酶转化为其完全芳香族形式，这可能有助于解释这些物质的致突变和致癌活性。对9,10 - 二氢苯并[a]芘（9,10 - DHB[a]P）代谢转化为苯并[a]芘（B[a]P）以及9 - 和/或10 - 羟基 - 9,10 - DHB[a]P（OH - 9,10 - DHB[a]P）进行了定量测定。在β - 萘黄酮诱导的大鼠肝微粒体中，9,10 - DHB[a]P代谢生成B[a]P，其比活性为1.51 nmol B[a]P形成/分钟/毫克微粒体蛋白。B[a]P的形成与孵育时间和微粒体蛋白浓度直接相关。同样，9,10 - DHB[a]P转化为OH - 9,10 - DHB[a]P的比活性为4.48 nmol OH - 9,10 - DHB[a]P形成/分钟/毫克微粒体蛋白。其形成与孵育时间和微粒体蛋白浓度直接相关。文中讨论了OH - 9,10 - DHB[a]P作为B[a]P代谢中间体的可能性。
