ENVIRONMENTAL EFFECTS ON SIGNAL TRANSDUCTION

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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.