Oxidative Metabolism of Estrone Modified by Genistein and Bisphenol A in Rat Liver Microsomes

Genistein, the main isoflavone from soy, and bisphenol A (BPA), a food contaminant, are considered ubiquitous xenoestrogens. Here we investigated the influence of genistein and BPA on estrone (E1) metabolism in rat liver microsomes. Both substances inhibited the 2-hydroxylation and 16α-hydroxylation of E1, but in different degrees, thereby reducing the 2-OH-E1/16α-OH-E1 ratio, a biomarker for the risk of breast cancer. Although the 2-OH-E1/16α-OH-E1 ratio was lower under BPA treatment than under the control condition, the difference was not statistically significant. The 2-OH-E1/16α-OH-E1 ratio was significantly reduced by genistein treatment (P<0.05), and this effect was more pronounced when using a combination of BPA and genistein (P<0.01). Our findings suggest that a synergistic inhibition effect of genistein and BPA on E1 metabolism is associated with an increased risk of breast cancer.