Synthesis of Tobacco-SpecificN-Nitrosamines and Their Metabolites and Results of Related Bioassays
- 1 January 1996
- journal article
- review article
- Published by Taylor & Francis in Critical Reviews in Toxicology
- Vol. 26 (2) , 139-147
- https://doi.org/10.3109/10408449609017927
Abstract
Tobacco-specificN-nitrosamines (TSNA) are the most abundant, strong carcinogens in tobacco smoke. Seven TSNA have been identified in tobacco products:Nω-nitrosonornicotine (NNN),Nω-nitrosoanabasine (NAB),N-nitrosoanatabine (NAT), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL), and 4-(methylnitrosamino)-4-3-pyridyl)butyric acid (iso-NNAC). The syntheses of these compounds are reviewed. The syntheses of14C- and3H-labeled NNK as well as metabolites of NNK and NNN are also discussed. Comparative assays for lung tumorigenesis in femaleN mice were carried out for six of the TSNA and for two related compounds,N-nitrosodimethylamine (NDMA) andN-nitrosopyrrolidine (NPYR). They yielded the following ranking of potency: NDMA>NNK>NNAL> NPYR>NNN>NAB.Iso-NNAL andiso-NNAC were inactive. These results are also compared with previous assays of TSNA carcinogenicity in rats and hamsters.Keywords
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