Molecular Analysis of Isoflavonoid Genotoxicity

Abstract

Overall objective of our research project is to analyze, at the molecular level, the genotoxic effects of genistein, the main isoflavonoid in soybeans. Due to their anti-oxidative properties, soy isoflavonoids have received considerable attention as health food supplements. Recent studies have also documented a variety of other biological effects of isoflavonoids including anticancer activity. Some of these effects are due to structural similarity of genistein with steroid hormones, and some effects are thought to be due to the ability of genistein to interfere with cellular pathways involved in drug metabolism or cell cycle progression. However, it is unclear if the observed toxicity of genistein toward some types of cancer cells is specific and limited only to the cancer cells. Moreover, reasons for the genotoxic effects of genistein remain unexplained. We hypothesize that the genotoxic effects of isoflavonoids are mediated via damage to cellular DNA and subsequent modulation of the DNA damage repair pathways of the host cells. Fully understanding molecular mechanisms of the genotoxic effects of genistein will significantly improve utility of genistein and other isoflavones as pharmaceutical/neutraceutical compounds. Therefore, we are evaluating the genotoxic effects of genistein in rats as an animal model using Poly-ADP-ribose polymerase as a marker of DNA damage. This poster outlines the rationale, experimental approaches and preliminary results of our studies.