GST polymorphism and excretion of heterocyclic aromatic amine and isothiocyanate metabolites after Brassica consumption.
GST polymorphism and excretion of heterocyclic aromatic amine and isothiocyanate metabolites after Brassica consumption.
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DOI：
10.1002/em.20456
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发表时间：
2009-04
影响因子：
2.8
通讯作者：
Hebert, James R.
中科院分区：
文献类型：
--
作者：
Steck, Susan E.;Hebert, James R.
在流行病学研究中，芸苔属蔬菜摄入量与降低风险有关，而全熟肉类摄入量与多器官部位癌症风险增加有关。实验研究表明，I相和II相代谢酶的调节作用是这些关联的一种机制。杂环芳香胺（哈斯）是在高温下煮熟的肉类中形成的致癌物质。I相代谢酶催化哈斯的活化，II相代谢酶用于解毒活性致癌物。谷胱甘肽S-转移酶（GSTs）是一类II相代谢酶家族，其由芸苔属蔬菜中发现的植物化学物质异硫氰酸酯（ITCs）诱导并起缀合作用。这篇综述总结了人类喂养研究的结果，研究GST的多态性对ITC代谢产物排泄的影响，回顾了ITCs对HAA致突变性的调节证据，并讨论了喂养研究的必要性，研究编码I相和II相代谢酶的多态性基因之间的潜在相互作用，肉类摄入量和芸苔属植物摄入量，以阐明它们在癌症病因学中的作用。
Brassica vegetable intake has been associated with decreased risk and well-done meat intake has been associated with increased risk of cancers at multiple organ sites in epidemiologic studies. Experimental studies suggest a role of modulation of phase I and phase II metabolizing enzymes as one mechanism for these associations. Heterocyclic aromatic amines (HAAs) are carcinogens formed in meat that has been cooked to well-done and at high temperatures. Phase I metabolizing enzymes catalyze the activation of HAAs, and phase II metabolizing enzymes serve to detoxify the active carcinogens. The glutathione S-transferases (GSTs) are a family of phase II metabolizing enzymes that are induced by, and act to conjugate, isothiocyanates (ITCs), phytochemicals found in Brassica vegetables. This review summarizes the results of feeding studies in humans that examine effects of polymorphisms in GSTs on ITC metabolite excretion, reviews the evidence for modulation of HAA mutagenicity by ITCs, and discusses the need for feeding studies examining potential interactions among polymorphic genes encoding phase I and phase II metabolizing enzymes, meat intake, and Brassica intake to elucidate their role in cancer etiology.
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