A STUDY OF GST GENOTYPES AND METABOLISM OF ISOTHIOCYANATES (ITCS) IN HUMANS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 异硫氰酸酯(ITCs)及其结合物在动物模型中是有效的抑制肺癌发生的药物。ITCs的化学预防活性主要归因于选择性抑制细胞色素P450和诱导II相酶。近年来，细胞培养研究显示了ITCs抑制肿瘤的一个潜在的重要新机制，包括通过激活信号转导通路诱导细胞凋亡和细胞周期停滞。这些研究表明，如果在启动后阶段给药，ITCs可能会抑制肿瘤的发生。最近的一项流行病学研究表明，ITC的摄入量对GSTM1和GSTT1零基因携带者具有高度保护作用。本研究旨在探讨谷胱甘肽转移酶(GST)基因多态性在人类ITC代谢中的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Isothiocyanates (ITCs) and their conjugates are effective inhibitors against lung tumorigenesis in animal models. The chemopreventive activities of ITCs have been attributed mainly to selective inhibition of cytochrome-P450s and induction of phase II enzymes. In recent years, cell culture studies have shown a potentially important new mechanism of tumor inhibition by ITCs, involving induction of apoptosis and cell cycle arrest mediated through activation of signal transduction pathways. These studies suggested that ITCs may inhibit tumorigenesis when administered during post-initiation phases. A recent epidemiological study has shown that ITC intake is highly protective in individuals with GSTM1 and GSTT1 null genotypes. This study is designed to investigate the role of glutathione transferase (GST) polymorphism in ITC metabolism in humans.