SELENIUM METABOLISM AND ANTICARCINOGENIC ACTION

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The identification of novel selenium compounds that have good chemopreventive activity and low toxicity is of great potential benefit. We have uncovered important determinants of these effects that resulted in the discovery of a new class of chemopreventive compounds. These compounds provide a means for relatively straightforward exploration of mechanisms of chemopreventive action compared to other organoselenium compounds that show less metabolic stability. It is proposed that lipophilic derivatives of selenium and sulfur are produced through known biochemical reactions to create similar types of chemopreventive compounds. The purpose of this study is to synthesize novel organoselenium compounds for testing, study their metabolism in the whole animal to correlate critical metabolites with chemopreventive activity, and define the biochemical origin of critical metabolites in cell-free systems. The long-term goal is to develop improved chemopreventive compounds of low toxicity for possible long-term use in humans. This work will lead to a better understanding of chemopreventive mechanisms of selenium. It also provides an important conceptual advance in understanding how chemopreventive activity can be developed and enhanced during the metabolism of selenium or sulfur in plants and animals.