Inhibition of Mitochondrial Estrogen Metabolism as a Possible Mechanism of Breast Cancer Prevention
Annual rept. 1 Jul 1999-30 Jun 2000
FLORIDA AGRICULTURAL AND MECHANICAL UNIV TALLAHASSEE
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Breast cancer is the second leading cause of cancer-related deaths for women . Estrogen metabolism as well as mitochondrial alterations are associated with cancer. We propose that the mitochondrial metabolism of estrogens play a major role in the induction of cancer. We hypothesize that diethylstilbestrol DES is metabolized by the mitochondria to DES quinone which causes DNA alterations associated with cancer. We further propose that Diallyl Sulfide DAS will inhibit this metabolism. To test this hypothesis we isolated mitochondria, microsomes, and nuclei from the breast tissue of female ACI rats. UV analysis revealed that all three organelles catalyzed the oxidation and reduction of DES. DAS was shown to inhibit these reactions by as much as 50. These results were confirmed by HPLC analysis. These results suggest that metabolism of estrogens may play a critical role in estrogen induced breast cancer. DAS and similar chemicals may inhibit the formation of breast cancer by inhibiting estrogen metabolism. This study provides a rationale for more studies on DAS and similar chemicals on the prevention of breast cancer.
- Medicine and Medical Research