EFFECTS OF LOW-DOSE CADMIUM ON PROSTATE CELLS

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DESCRIPTION (Adapted from Applicant's Abstract): Chronic low-level exposure to environmental toxins, including cadmium, is an enormous and growing problem in the industrialized world. cadmium is a potent carcinogen in rodents and has also been linked to human lung and prostate cancer, a malignant disease with an increasing mortality. In vitro models of experimental cadmium toxicity is proposed to study the molecular mechanisms of prostate epithelia cell injury and repair. One promising strategy for protection from toxins is the use of low doses of chemicals to enhance cell tolerance and recovery, a phenomenon known as hormesis. This strategy is also the theoretical basis for the observed effects in homeopathy. The homeopathic literature has for decades reported the use of cadmium for the treatment of cancer. Low and very-low-dose cadmium doses induce gene expression of protective proteins (metallothonein (MT) and heat shock) and reduce mortality to toxic doses both in vitro and in vivo. In preliminary research it was demonstrated that medium dose cadmium exposure altered gene expression patterns, enhanced protective protein (MT) levels and protected against acute cadmium toxicity in human prostate epithelial cells. The objective of this project is to determine the tissue specific molecular signatures produced by low dose levels of cadmium and to identify the optimal doses that protect against toxic injury. When completed we will have developed a novel and highly sensitive approach for detecting and treating toxic exposures. We will also have developed, for the first time, a systematic model for the scientific study of protective hormesis and homeopathy in environmental toxicology and prostate disease.