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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 异硫氰酸酯（ITC）及其缀合物是动物模型中抗肺肿瘤发生的有效抑制剂。 ITCs的化学预防活性主要归因于细胞色素P450的选择性抑制和II相酶的诱导。 近年来，细胞培养研究显示了ITCs抑制肿瘤的一种潜在的重要新机制，涉及通过激活信号转导途径介导的凋亡诱导和细胞周期阻滞。 这些研究表明，ITC可以抑制肿瘤发生时，在启动后阶段的管理。 最近的一项流行病学研究表明，ITC摄入量对GSTM 1和GSTT 1缺失基因型的个体具有高度保护作用。 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.