Tobacco-related-compound-induced Nitrosative Stress Injury in the Hamster Cheek Pouch

• Published in: Journal of dental research Vol. 83; no. 12; pp. 903 - 908
• Main Authors: Barley, R.D.C., Pollock, S., Shallow, M.C., Peters, E., Lam, E.W.N.
• Format: Journal Article
• Language: English
• Published: United States SAGE Publications 01-12-2004; SAGE PUBLICATIONS, INC
• Subjects: Animals; Carcinogens - adverse effects; Cell Survival - drug effects; Cells, Cultured; Chromatin - drug effects; Cricetinae; DNA Damage; DNA, Single-Stranded - drug effects; Dose-Response Relationship, Drug; Mesocricetus; Mouth Mucosa - drug effects; Mouth Mucosa - pathology; Nicotine - adverse effects; Nitrosamines - adverse effects; Oxidative Stress - drug effects; Peroxynitrous Acid - adverse effects; Tobacco, Smokeless - adverse effects; Tyrosine - analogs & derivatives; Tyrosine - analysis; tobacco-related compounds; oral mucosa; protein nitrosation; DNA damage
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/154405910408301203

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.