An alternatively spliced cytochrome P4501A1 in human brain fails to bioactivate polycyclic aromatic hydrocarbons to DNA-reactive metabolites
An alternatively spliced cytochrome P4501A1 in human brain fails to bioactivate polycyclic aromatic hydrocarbons to DNA-reactive metabolites
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DOI：
10.1111/j.1471-4159.2007.04599.x
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发表时间：
2007-08-01
影响因子：
4.7
通讯作者：
Ravindranath, Vijayalakshmi
中科院分区：
文献类型：
--
作者：
Kommaddi, Reddy P.;Turman, Cheri M.;Ravindranath, Vijayalakshmi
CYP 1A 1是一种细胞色素P450酶，可将多环芳烃代谢为遗传毒性代谢物，与DNA结合并启动致癌作用。对CYP 1A 1的完整开放阅读框的RT-PCR扩增产生了1593 bp的扩增子，其具有翻译成功能性P450酶的外显子-6的87 bp缺失。与野生型CYP 1A 1不同，外显子6 del CYP 1A 1不代谢多环芳烃，如苯并（a）芘，形成DNA加合物的遗传毒性，最终致癌物。与野生型CYP 1A 1相比，外显子6 del CYP 1A 1代谢乙氧基试卤灵（CYP 1A 1的经典底物）的效率较低，而戊氧基和苄氧基试卤灵（CYP 2B的经典底物）的脱烷基化效率更高。计算机对接
CYP1A 1, a cytochrome P450 enzyme, metabolizes polycyclic aromatic hydrocarbons to genotoxic metabolite(s) that bind to DNA and initiate carcinogenesis. RT-PCR amplification of the complete open reading frame of CYP1A1 generated an amplicon of 1593 bp having deletion of 87 bp of exon-6 that translated into functional P450 enzyme. Unlike wild type CYP1A1, exon 6 del CYP1A1 did not metabolize polycyclic aromatic hydrocarbons such as, benzo(a)pyrene to genotoxic, ultimate carcinogens that form DNA adducts. Exon 6 del CYP1A1 metabolized ethoxyresorufin (the classical substrate for CYP1A1) less efficiently compared with wild type CYP1A1 while pentoxy and benzyloxyresorufin (classical substrates for CYP2B) were dealkylated more efficiently. In silico docking