Tobacco-related-compound-induced Nitrosative Stress Injury in the Hamster Cheek Pouch
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 cy...
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| Published in: | Journal of dental research Vol. 83; no. 12; pp. 903 - 908 |
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| Format: | Journal Article |
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01-12-2004
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| 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. |
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| AbstractList | The nitric oxide radical ( super(.)NO) released from tobacco-related compounds induces DNA damage, protein modifications, and cellular toxicity through the formation of peroxynitrite (ONOO super(-)), the reaction product of super(.)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 super(-) 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 super(-) damage in intact hamster cheek pouch tissues. 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. 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. 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. |
| Author | Shallow, M.C. Lam, E.W.N. Peters, E. Barley, R.D.C. Pollock, S. |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/15557395$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1177/00220345010800021401 10.1016/S0076-6879(99)01101-5 10.1084/jem.181.4.1333 10.1007/s00405-002-0498-2 10.1016/S0300-483X(02)00357-8 10.1186/1617-9625-1-3-207 10.1111/j.1600-0714.1985.tb00501.x 10.1096/fj.00.011rev 10.1016/S0278-6915(98)00070-2 10.1016/S0076-6879(99)01109-X 10.1093/carcin/10.11.1997 10.1126/science.276.5321.2034 10.1002/(SICI)1097-0347(200001)22:1<64::AID-HED10>3.0.CO;2-J 10.1016/S0378-4347(00)81033-6 10.1073/pnas.220207697 10.1177/00220345000790061001 10.1016/S0278-2391(96)90445-0 10.1111/j.1600-0714.1994.tb00054.x 10.1016/S0021-9258(17)36703-0 10.1152/ajpcell.1996.271.5.C1424 10.1006/abbi.1998.0755 10.1038/nm0695-546 10.1016/S0378-4274(02)00507-6 10.1089/15230860152409095 10.1161/01.HYP.12.4.365 10.1016/0022-1759(83)90303-4 |
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| Keywords | tobacco-related compounds oral mucosa protein nitrosation DNA damage |
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| Snippet | The nitric oxide radical (•NO) released from tobacco-related compounds induces DNA damage, protein modifications, and cellular toxicity through the formation... The nitric oxide radical (*NO) released from tobacco-related compounds induces DNA damage, protein modifications, and cellular toxicity through the formation... The nitric oxide radical ( • NO) released from tobacco-related compounds induces DNA damage, protein modifications, and cellular toxicity through the formation... The nitric oxide radical ( super(.)NO) released from tobacco-related compounds induces DNA damage, protein modifications, and cellular toxicity through the... |
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| SubjectTerms | 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 |
| Title | Tobacco-related-compound-induced Nitrosative Stress Injury in the Hamster Cheek Pouch |
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