TY - JOUR
T1 - Synthesis of tobacco-specific N-nitrosamines and their metabolites and results of related bioassays
AU - Amin, Shantu
AU - Desai, Dhimant
AU - Hecht, Stephen S.
AU - Hoffmann, Dietrich
N1 - Funding Information:
Our studies are supported by grants CA-29580, CA-44377, andNO1-CP-21 I15 from the U.S. National Cancer Institute.
PY - 1996
Y1 - 1996
N2 - Tobacco-specific N-nitrosamines (TSNA) are the most abundant, strong carcinogens in tobacco smoke. Seven TSNA have been identified in tobacco products: N'-nitrosonornicotine (NNN), N'-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 of 14C- and 3H-labeled NNK as well as metabolites of NNK and NNN are also discussed. Comparative assays for lung tumorigenesis in female A/J mice were carried out for six of the TSNA and for two related compounds, N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR). They yielded the following ranking of potency: NDMA>NNK>NNAL> NPYR>NNN>NAB. Iso-NNAL and iso-NNAC were inactive. These results are also compared with previous assays of TSNA carcinogenicity in rats and hamsters.
AB - Tobacco-specific N-nitrosamines (TSNA) are the most abundant, strong carcinogens in tobacco smoke. Seven TSNA have been identified in tobacco products: N'-nitrosonornicotine (NNN), N'-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 of 14C- and 3H-labeled NNK as well as metabolites of NNK and NNN are also discussed. Comparative assays for lung tumorigenesis in female A/J mice were carried out for six of the TSNA and for two related compounds, N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR). They yielded the following ranking of potency: NDMA>NNK>NNAL> NPYR>NNN>NAB. Iso-NNAL and iso-NNAC were inactive. These results are also compared with previous assays of TSNA carcinogenicity in rats and hamsters.
UR - http://www.scopus.com/inward/record.url?scp=0029968631&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029968631&partnerID=8YFLogxK
U2 - 10.3109/10408449609017927
DO - 10.3109/10408449609017927
M3 - Review article
C2 - 8688157
AN - SCOPUS:0029968631
VL - 26
SP - 139
EP - 147
JO - Critical Reviews in Toxicology
JF - Critical Reviews in Toxicology
SN - 1040-8444
IS - 2
ER -