| dc.description.abstract | Many studies show that estradiol (E2) and consumption of soy and its primary phytoestrogen component genistein (GEN) can inhibit the formation of colon tumors. However, the effects of E2 and GEN at physiologically relevant levels in non-diseased colonocytes have yet to be investigated. We hypothesized that E2 and GEN could prove to be chemo-protective agents in the colon by moderately increasing apoptosis and decreasing proliferation in a healthy system. Thus, the presented studies focused on evaluating the effects of E2 and GEN in non-malignant colonocytes in vitro and in vivo to determine how the compounds influence the physiology of these cells. E2 (1 nM/L) and GEN treatments (1 and 10 microM/L) decreased cell growth, increased apoptosis, and increased p53 transcriptional activity in young adult mouse colonocytes, a non-malignant cell line. To study further the effects of E2 and GEN in healthy colonic epithelia, we evaluated physiologic changes in colonic crypts in ovariectomized mice given an E2 pellet, 1,000 ppm GEN diet, or a phytoestrogen free diet. As seen in vitro, E2 treated animals had significantly higher rates of apoptosis with GEN trending in the same fashion. These data demonstrate that E2 and GEN alter the physiology of non-malignant colonocytes.
Collectively, with our previous data, this suggests that E2 and GEN influence colonocyte physiology and this state may partially explain how these compounds decrease risk of colon cancer. | en |
