title: Dietary antioxidants fail in protection against oxidative genetic damage in in vitro evaluation.
abstract: Carcinogenesis is believed to be induced through the oxidative damage of DNA, and antioxidants are expected to suppress it. So, the polyphenolic antioxidants in daily foods were investigated to see whether they protect against genetic damage by active oxygen. In the evaluation, we used a bioassay and a chemical determination, a Salmonella mutagenicity test for mutation by a N-hydroxyl radical from one of the dietary carcinogens 3-amino-1-methyl-5H-pyrido[4,3-b]indole and the formation of 8-hydroxyl (8-OHdG) from 2'-deoxyguanosine (2'-dG) in a Fenton OH-radical generating system. Thirty-one antioxidants including flavonoids were compared in terms of radical-trapping activity with bacterial DNA and 2'-dG. Antioxidants inhibited the mutation but the IC50 values were in the mM order. Against 8-OHdG formation, only alpha-tocopherol had a suppressive effect with an IC50 of 1.5 microM. Thus, except alpha-tocopherol, the dietary antioxidants did not scavenge the biological radicals faster than bacterial DNA and intact 2'-dG, indicating that they failed to prevent oxidative gene damage and probably carcinogenesis.
authors.affiliation: Department of Life Science, Graduate School of Science and Technology, Kobe University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sun
authors.forename: H
authors.initials: H
authors.lastname: Sakakibara
authors.forename: H
authors.initials: H
authors.lastname: Ashida
authors.forename: G
authors.initials: G
authors.lastname: Danno
authors.forename: K
authors.initials: K
authors.lastname: Kanazawa
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D015764:Bepridil / Q000031:analogs & derivatives* / Q000378:metabolism; D001713:Biphenyl Compounds; D002243:Carbolines / Q000494:pharmacology; D004269:DNA, Bacterial / Q000187:drug effects* / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005419:Flavonoids; D016166:Free Radical Scavengers / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000494:pharmacology; D009152:Mutagenicity Tests; D010636:Phenols / Q000494:pharmacology*; D010851:Picrates; D011108:Polymers / Q000494:pharmacology*; D059808:Polyphenols; D012475:Salmonella / Q000187:drug effects / Q000235:genetics
chemical_list: D016587:Antimutagenic Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D002243:Carbolines; D004269:DNA, Bacterial; D005419:Flavonoids; D016166:Free Radical Scavengers; D010636:Phenols; D010851:Picrates; D011108:Polymers; D059808:Polyphenols; D017665:Hydroxyl Radical; C027210:3-hydroxyamino-1-methyl-5H-pyrido(4,3-b)indole; D015764:Bepridil; D000080242:8-Hydroxy-2'-Deoxyguanosine; C004931:1,1-diphenyl-2-picrylhydrazyl; D003849:Deoxyguanosine