title: Cellular DNA breakage by soy isoflavone genistein and its methylated structural analogue biochanin A.
abstract: Epidemiological studies have indicated that populations with high isoflavone intake through soy consumption have lower rates of breast, prostate, and colon cancer. The isoflavone polyphenol genistein in soybean is considered to be a potent chemopreventive agent against cancer. In order to explore the chemical basis of chemopreventive activity of genistein, in this paper we have examined the structure-activity relationship between genistein and its structural analogue biochanin A. We show that both genistein and its methylated derivative biochanin A are able to mobilize nuclear copper in human lymphocyte, leading to degradation of cellular DNA. However, the relative rate of DNA breakage was greater in the case of genistein. Further, the cellular DNA degradation was inhibited by copper chelator (neocuproine/bathocuproine) but not by compounds that specifically bind iron and zinc (desferrioxamine mesylate and histidine, respectively). We also compared the antioxidant activity of the two isoflavones against tert-butylhydroperoxide-induced oxidative breakage in lymphocytes. Again genistein was found to be more effective than biochanin A in providing protection against oxidative stress induced by tert-butylhydroperoxide. It would therefore appear that the structural features of isoflavones that are important for antioxidant properties are also the ones that contribute to their pro-oxidant action through a mechanism that involves redox cycling of chromatin-bound nuclear copper.
authors.affiliation: Department of Biochemistry, AMU, Aligarh, Uttar Pradesh, India.
authors.forename: Mohd Fahad
authors.initials: MF
authors.lastname: Ullah
authors.forename: Uzma
authors.initials: U
authors.lastname: Shamim
authors.forename: Sarmad
authors.initials: S
authors.lastname: Hanif
authors.forename: Asfar S
authors.initials: AS
authors.lastname: Azmi
authors.forename: Sheikh M
authors.initials: SM
authors.lastname: Hadi
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D020552:Comet Assay; D003300:Copper / Q000378:metabolism; D053960:DNA Breaks; D016166:Free Radical Scavengers / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D003300:Copper; D006861:Hydrogen Peroxide; D019833:Genistein; C004541:biochanin A