title: Antioxidant induces DNA damage, cell death and mutagenicity in human lung and skin normal cells.
abstract: Clinical trials have shown that antioxidant supplementation increased the risk of lung and skin cancers, but the underlying molecular mechanism is unknown. Here, we show that epigallocatechin gallate (EGCG) as an exemplary antioxidant induced significant death and DNA damage in human lung and skin normal cells through a reductive mechanism. Our results show direct evidence of reductive DNA damage in the cells. We found that EGCG was much more toxic against normal cells than H₂O₂ and cisplatin as toxic and cancer-causing agents, while EGCG at low concentrations (≤100 μM) increased slightly the lung cancer cell viability. EGCG induced DNA double-strand breaks and apoptosis in normal cells and enhanced the mutation frequency. These results provide a compelling explanation for the clinical results and unravel a new reductive damaging mechanism in cellular processes. This study therefore provides a fresh understanding of aging and diseases, and may lead to effective prevention and therapies.
authors.affiliation: Department of Physics and Astronomy and Departments of Biology and Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Linda Y
authors.initials: LY
authors.lastname: Lu
authors.forename: Ning
authors.initials: N
authors.lastname: Ou
authors.forename: Qing-Bin
authors.initials: QB
authors.lastname: Lu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology / Q000633:toxicity; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D020128:Inhibitory Concentration 50; D016296:Mutagenesis / Q000187:drug effects*; D009154:Mutation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology / Q000633:toxicity; D013662:Tea / Q000737:chemistry
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D013662:Tea; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D007041:Hypoxanthine Phosphoribosyltransferase