细胞色素P450酶在内源信号通路和环境致癌作用中的作用。
The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis.
作者信息
Nebert Daniel W, Dalton Timothy P
机构信息
Department of Environmental Health, and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, Ohio 45267-0056, USA.
出版信息
Nat Rev Cancer. 2006 Dec;6(12):947-60. doi: 10.1038/nrc2015.
Some cytochrome P450 (CYP) heme-thiolate enzymes participate in the detoxication and, paradoxically, the formation of reactive intermediates of thousands of chemicals that can damage DNA, as well as lipids and proteins. CYP expression can also affect the production of molecules derived from arachidonic acid, and alters various downstream signal-transduction pathways. Such changes can be precursors to malignancy. Recent studies in mice have changed our perceptions about the function of CYP1 enzymes. We suggest a two-tiered system to predict an overall inter-individual risk of tumorigenesis based on DNA variants in certain 'early defence' CYP genes, combined with polymorphisms in various downstream target genes.
一些细胞色素P450（CYP）血红素硫醇盐酶参与解毒过程，然而矛盾的是，它们也参与数千种化学物质活性中间体的形成，这些中间体可损伤DNA、脂质和蛋白质。CYP的表达还会影响源自花生四烯酸的分子的产生，并改变各种下游信号转导途径。这些变化可能是恶性肿瘤的先兆。最近对小鼠的研究改变了我们对CYP1酶功能的认识。我们提出了一个两层系统，根据某些“早期防御”CYP基因中的DNA变异，结合各种下游靶基因中的多态性，来预测个体发生肿瘤的总体风险。
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