ENVIRONMENTAL EFFECTS ON SIGNAL TRANSDUCTION

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。 博士拉斯金目前的研究兴趣是了解饮食营养素在前列腺癌发展中的作用。 特别是，他一直在表征前列腺中致癌物的生物活化，前列腺是一种细胞色素P450活性有限的组织。他已经确定了前列腺营养素的一种新的分子靶点，这是一种将前列腺致癌物质氧化为DNA反应性代谢物并产生细胞氧化应激的蛋白质。几种重要的营养物质，特别是阿魏酸，香草酸和表没食子儿茶素没食子酸酯，是这种酶的有效和强效的抑制剂，可以抑制应激反应，这可能是其化学预防活性的重要机制。 在BRC中，拉斯金博士一直在使用各种不同的细胞类型，包括前列腺肿瘤细胞来表征氧化应激的过程。 在这些利用自参考氧传感器的研究中，主要的努力集中在确定单个细胞和/或细胞单层的氧利用是否与来自周围环境的氧扩散相匹配。 还启动了研究以确定细胞是否能够从缺氧中恢复，缺氧是氧化应激反应的主要贡献者。

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. Dr. Laskin's current research interests are in understanding the role of dietary nutrients in the development of prostate cancer. In particular, he has been characterizing bioactivation of carcinogens in the prostate, a tissue with limited cytochrome P450 activity. He has identified a novel molecular target for nutrients in the prostate, which is a protein that oxidizes prostate carcinogens to DNA-reactive metabolites and generates cellular oxidative stress. Several important nutrients, in particular, ferulic acid, vanillic acid and epigallocatechin gallate, are effective and potent inhibitors of this enzyme and may suppress the stress response and this may be an important mechanism of their chemoreventative activity. In the BRC, Dr. Laskin has been using a variety of different cell types including prostate tumor cells to characterize the process of oxidative stress. In these studies, which utilized self-referencing oxygen sensors, a major effort has focused on determining if oxygen utilization by individual cells and/or cell monolayers, matches diffusion of oxygen from the surrounding environment. Studies were also initiated to determine if cells are able to recover from hypoxia, a major contributor to the oxidative stress response.