Ozawa S
Department of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
Yakugaku Zasshi. 1997 Nov;117(10-11):895-909. doi: 10.1248/yakushi1947.117.10-11_895.
Xenobiotic metabolizing enzymes are known to play a role in the metabolic activation of environmental mutagens and carcinogens to exert their carcinogenic effects as well as detoxification by increasing their hydrophilicity. These enzymes include cytochrome P450s, glutathione S-transferases (GSTs), acetyltransferases (NATs) and sulfotransferases. Genetic polymorphisms in many of these enzymes, such as CYP1A1, CYP1A2, CYP2C9, CYP2D6, CYP2E1, NAT1, NAT2, GSTM1, GSTP1 and GSTT1, have been shown to occur, which result in the altered expression of enzymatic activities. This suggests that the genetic polymorphisms may affect the individual susceptibility to environmental carcinogens and thus play a role in human carcinogenesis. Recently, the mutations that confer those polymorphisms of xenobiotic metabolizing enzymes have been identified and genotyping methods for the genetic polymorphisms have been developed. Specific phenotypes and genotypes for CYP1A1, CYP2D6, CYP2E1, NAT1, NAT2, GSTM1 and GSTP1 have been associated with susceptibility to malignant diseases including lung, bladder and colon cancers, although the association was not confirmed in some studies. A number of factors such as degree of exposure to environmental carcinogens and the role of xenobiotic metabolizing enzymes in human carcinogenesis should carefully be evaluated in understanding genetic susceptibility.
已知外源性代谢酶在环境诱变剂和致癌物的代谢活化中发挥作用，使其发挥致癌作用，同时通过增加其亲水性进行解毒。这些酶包括细胞色素P450、谷胱甘肽S-转移酶（GSTs）、乙酰转移酶（NATs）和磺基转移酶。已证明其中许多酶存在基因多态性，如CYP1A1、CYP1A2、CYP2C9、CYP2D6、CYP2E1、NAT1、NAT2、GSTM1、GSTP1和GSTT1，这会导致酶活性表达改变。这表明基因多态性可能影响个体对环境致癌物的易感性，从而在人类致癌过程中发挥作用。最近，已鉴定出赋予外源性代谢酶这些多态性的突变，并开发了针对基因多态性的基因分型方法。尽管在一些研究中未得到证实，但CYP1A1、CYP2D6、CYP2E1、NAT1、NAT2、GSTM1和GSTP1的特定表型和基因型与包括肺癌、膀胱癌和结肠癌在内的恶性疾病易感性有关。在理解遗传易感性时，应仔细评估许多因素，如环境致癌物的暴露程度以及外源性代谢酶在人类致癌过程中的作用。
