title: Tobacco-related-compound-induced nitrosative stress injury in the hamster cheek pouch.
abstract: The nitric oxide radical (*NO) released from tobacco-related compounds induces DNA damage, protein modifications, and cellular toxicity through the formation of peroxynitrite (ONOO-), the reaction product of *NO and the oxygen radical, superoxide. We hypothesize that tobacco-related compounds are cytotoxic and induce quantifiable DNA single-strand breaks in immortalized hamster cheek pouch (POII) cells, and that an amino acid marker of ONOO- injury, namely, 3-nitrotyrosine (3-NT), is detectable in hamster cheek pouch tissues chronically exposed to these compounds. We observed a dose-dependent decrease in POII cell viability with increasing tobacco-related compound concentrations, as well as a dose-dependent increase in DNA strand breaks. Semi-quantitative immunohistochemistry showed intense 3-NT immunoreactivity in hamster tissues treated with tobacco-related compounds compared with controls (p < 0.005). Our results suggest that tobacco-related compounds, including nicotine, are genotoxic, and that 3-NT is a quantifiable marker of ONOO- damage in intact hamster cheek pouch tissues.
authors.affiliation: Division of Oral & Maxillofacial Radiology, Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, DPC 2085, Edmonton, AB T6G 2N8, Canada.
authors.forename: R D C
authors.initials: RD
authors.lastname: Barley
authors.forename: S
authors.initials: S
authors.lastname: Pollock
authors.forename: M C
authors.initials: MC
authors.lastname: Shallow
authors.forename: E
authors.initials: E
authors.lastname: Peters
authors.forename: E W N
authors.initials: EW
authors.lastname: Lam
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000009:adverse effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects; D006224:Cricetinae; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000187:drug effects* / Q000473:pathology; D009538:Nicotine / Q000009:adverse effects; D009602:Nitrosamines / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000009:adverse effects; D014030:Tobacco, Smokeless / Q000009:adverse effects*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D002273:Carcinogens; D002843:Chromatin; D004277:DNA, Single-Stranded; D009602:Nitrosamines; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D009538:Nicotine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C008655:N'-nitrosonornicotine