Reduction of genistein clastogenicity in Chinese hamster V79 cells by daidzein and other flavonoids.
A broad spectrum of health benefits has been ascribed to soy products. These products contain soy protein and relatively high levels of polyphenolic compounds known as flavonoids. While they are the most likely candidates for biological activity, flavonoids as a class, and of specific interest, genistein, are well known to be genotoxic due to their ability to "poison" cellular DNA topoisomerase II (topo II) resulting in stable chromosome breakage and mutation and raising questions about the long term health effects associated with chronic flavonoid exposure. Interestingly, some flavonoids, such as biochanin, galangin and daidzein, are catalytic topo II inhibitors (not poisons) and actually antagonize the clastogenicity of topo II poisons. It is shown in the present paper that flavonoids possessing catalytic topo II inhibitory activity, strongly antagonize the clastogenicity of genistein in Chinese hamster V79 cells. Importantly, one of these, daidzein, is a major constituent of marketed soy products. It is conjectured that the potential human clastogenic risk of soy products containing genistein might be mitigated or abolished due to the presence of daidzein or other flavonoids in those products.
Snyder
Ronald D
RD
Bristol-Myers Squibb Pharma Company, PO Box 50, DE 19714 Newark, UK. ronald.snyder@spcorp.com
Gillies
Peter J
PJ
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D019587:Dietary Supplements; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D005452:Fluoresceins; D019833:Genistein / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007529:Isoflavones / Q000494:pharmacology*; D015162:Micronucleus Tests; D009153:Mutagens / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D059005:Topoisomerase II Inhibitors
D004791:Enzyme Inhibitors; D005419:Flavonoids; D005452:Fluoresceins; D007529:Isoflavones; D009153:Mutagens; D017382:Reactive Oxygen Species; D059005:Topoisomerase II Inhibitors; C029569:diacetyldichlorofluorescein; C004742:daidzein; D019833:Genistein; D004121:Dimethyl Sulfoxide