Inhibition of Mitochondrial Estrogen Metabolism as a Possible Mechanism of Breast Cancer Prevention.

摘要

This project addresses the possible role of mitochondrial estrogen metabolism and its inhibition in mammary carcinogenesis of female ACI rats. Diethyistilbestrol (DES) have been shown to cause cancer in several animals species whereas diallyl sulfide (DAS) inhibits cancer. We hypothesis that DES is metabolized by the mitochondria to reactive metabolites producing DNA adducts. We further propose that DAS will prevent this metabolism thus prevent the production of DNA adducts. The results of this study demonstrates that organelles (mitochondria, microsomes, and nuclei) catalyze the oxidation and reduction of DES and diallyl sulfide inhibits this metabolism in a noncompetitive fashion. Furthermore, DAS inhibits the formation of mitochondrial DNA adducts in both in vitro and in vivo. The results of this study will help elucidate the mechanism of estrogen induced breast cancer. This data will provide a foundation for the further investigation of the chemopreventive properties of DAS and structurally similar compounds.