Document Detail

Oxygen radicals potentiate the genetic toxicity of tobacco-specific nitrosamines.
MedLine Citation:
PMID:  8448908     Owner:  NLM     Status:  MEDLINE    
Tobacco-specific nitrosamines (TSNAs), nitrosonornicotine (NNN) and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are metabolites of nicotine and the major carcinogens in cigarette smoke. To evaluate the effect of oxygen radicals on TSNA-induced genetic damage, MRC-5 fetal human lung cells were exposed to NNN and NNK (5 mM) and DNA single-strand breaks measured. Both NNN and NNK produced a dose-dependent increase in strand breaks up to 10 mM which was cytotoxic. In combination with enzymatically-generated oxygen radicals, strand breakage increased by approximately 50% for both NNN and NNK. Oxygen radical scavengers (superoxide dismutase, catalase, mannitol) significantly reduced the DNA damage caused by both the TSNAs and TSNAs plus oxygen radicals, suggesting that the genotoxicity is radical-mediated. Because both superoxide dismutase and catalase were protective, the hydroxyl radical may be playing an important role in the mediation of the DNA damage observed.
A B Weitberg; D Corvese
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical genetics     Volume:  43     ISSN:  0009-9163     ISO Abbreviation:  Clin. Genet.     Publication Date:  1993 Feb 
Date Detail:
Created Date:  1993-04-09     Completed Date:  1993-04-09     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0253664     Medline TA:  Clin Genet     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  88-91     Citation Subset:  IM    
Division of Hematology/Oncology, Roger Williams Cancer Center, Providence, RI 02908.
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MeSH Terms
Carcinogens / toxicity*
Cells, Cultured
DNA Damage
DNA, Single-Stranded / drug effects
Drug Synergism
Free Radical Scavengers
Free Radicals / toxicity
Lung / cytology
Mutagens / metabolism,  toxicity*
Nicotine / analogs & derivatives
Nitrosamines / metabolism,  toxicity*
Nucleic Acid Denaturation
Plants, Toxic*
Reactive Oxygen Species / toxicity*
Reg. No./Substance:
0/Carcinogens; 0/DNA, Single-Stranded; 0/Free Radical Scavengers; 0/Free Radicals; 0/Mutagens; 0/Nitrosamines; 0/Reactive Oxygen Species; 54-11-5/Nicotine; 64091-91-4/4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; 80508-23-2/N'-nitrosonornicotine

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