ENVIRONMENTAL EFFECTS ON SIGNAL TRANSDUCTION

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。 拉斯金博士目前的研究兴趣是了解饮食营养素在前列腺癌发生中的作用。特别是，他一直在描述前列腺癌组织中致癌物的生物激活，这是一种细胞色素P450活性有限的组织。他已经为前列腺中的营养物质确定了一个新的分子靶点，这是一种蛋白质，可以将前列腺癌物质氧化成DNA反应的代谢物，并产生细胞氧化应激。几种重要的营养素，特别是阿魏酸、香草酸和表没食子儿茶素没食子酸酯，是该酶的有效和强有力的抑制剂，并可能抑制应激反应，这可能是其化学修复活性的重要机制。在BRC中，拉斯金博士一直在使用包括前列腺癌细胞在内的各种不同类型的细胞来表征氧化应激的过程。在这些利用自参照氧传感器的研究中，主要工作集中在确定单个细胞和/或细胞单层对氧的利用是否与周围环境中的氧扩散相匹配。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.