Identification of cytochrome P450 isoforms involved in 1-hydroxylation of pyrene
Identification of cytochrome P450 isoforms involved in 1-hydroxylation of pyrene
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DOI：
10.1016/s0013-9351(03)00134-8
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发表时间：
2004-03-01
影响因子：
8.3
通讯作者：
Kawamoto, T
中科院分区：
文献类型：
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作者：
Kim, YD;Todoroki, H;Kawamoto, T
尿1-羟基芘（1-OHP）已被用作环境多环芳烃（PAH）暴露的生物标志物。然而，众所周知，芘代谢为1-OHP的过程中存在个体间差异，这取决于代谢酶的活性，尤其是细胞色素P450（CYP）。在这项研究中，我们研究了芘的1-羟基化的10种形式的cDNA表达的人P450，以确定参与芘的主要代谢途径的P450的主要亚型。芘的1-羟基化活性在0.5和50 μ M芘的CYP 1A 1中最高，其次是CYP 1B 1和1A 2，而其他酶，包括CYP 2A 6、2C 8、2C 9 *1、2C 19、2D 6、2 E1、3A 4和对照微粒体，显示出非常低或检测不到的1-羟基化速率。综上所述，CYP 1A 1、1B 1和1A 2是芘体外1-羟基化的主要代谢酶。这表明，这些酶的个体差异必须包括在流行病学研究中，以评估使用尿1-OHP的PAH暴露。(C)2003年爱思唯尔公司All rights reserved.
Urinary 1-hydroxypyrene (1-OHP) has been used as a biomarker for environmental polyaromatic hydrocarbon (PAH) exposure. However, it is known that there is an interindividual variability in metabolism of pyrene to 1-OHP depending on the activities of the metabolizing enzymes, especially cytochrome P450s (CYPs). In this study, we investigated the 1-hydroxylation of pyrene by 10 forms of cDNA-expressed human P450s in order to identify the principal isoforms of P450s that are involved in the major metabolic pathway of pyrene. The pyrene 1-hydroxylation activity was found to be the highest in CYP1A1 at both 0.5 and 50 muM of pyrene, followed by CYP1B1 and 1A2, whereas other enzymes, including CYP2A6, 2C8, 2C9*1, 2C19, 2D6, 2E1, 3A4, and control microsomes, showed very low or undetectable rates of 1-hydroxylation. In conclusion, CYP1A1, 1B1, and 1A2 are major metabolizing enzymes in 1-hydroxylation of pyrene in vitro. This suggests that the individual difference of these enzymes must be included in epidemiological studies to evaluate PAH exposure using urinary 1-OHP. (C) 2003 Elsevier Inc. All rights reserved.