DNA damage induced by hypochlorite and hypobromite with reference to inflammation-associated carcinogenesis.
Hypohalites (OCl-, OBr-) are formed at inflammation sites as antimicrobial agents. OCl- is also used for the disinfection of water supplies and the association of drinking chlorinated water with cancer risk is pointed out. In this study, OCl- itself induced 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, while OBr- damaged DNA only when glutathione (GSH) was added. OCl- caused oxidative DNA damage more efficiently than OBr-/GSH. In experiment with 32P-labeled DNA fragments, OCl- strongly caused piperidine-labile sites at guanine residues than piperidine-inert 8-oxodG, whereas OBr-/GSH caused no piperidine-labile sites. Endogenous OCl- may play a role in genotoxicity close to the site of inflammation.
Ohnishi
Shiho
S
Department of Hygiene, Mie University School of Medicine, 2-174, Edobashi, Tsu, Mie 514-8507, Japan.
Murata
Mariko
M
Kawanishi
Shosuke
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001959:Bromates / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D016147:Genes, Tumor Suppressor; D016158:Genes, p53 / Q000502:physiology; D011905:Genes, ras / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D009369:Neoplasms / Q000209:etiology*; D010084:Oxidation-Reduction; D010759:Phosphorus Isotopes; D010880:Piperidines / Q000378:metabolism; D012973:Sodium Hypochlorite / Q000494:pharmacology*
D001959:Bromates; D002273:Carcinogens; D010759:Phosphorus Isotopes; D010880:Piperidines; C032727:piperidine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D012973:Sodium Hypochlorite; D003849:Deoxyguanosine; D005978:Glutathione; C027664:hypobromous acid; D004121:Dimethyl Sulfoxide