Synthesis of tobacco-specific N-nitrosamines and their metabolites and results of related bioassays

Shantu Amin; Dhimant Desai; Stephen S. Hecht; Dietrich Hoffmann

doi:10.3109/10408449609017927

Synthesis of tobacco-specific N-nitrosamines and their metabolites and results of related bioassays

Shantu Amin, Dhimant Desai, Stephen S. Hecht, Dietrich Hoffmann

Research output: Contribution to journal › Review article › peer-review

35 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	139-147
Number of pages	9
Journal	Critical Reviews in Toxicology
Volume	26
Issue number	2
DOIs	https://doi.org/10.3109/10408449609017927
State	Published - 1996

Bibliographical note

Funding Information:
Our studies are supported by grants CA-29580, CA-44377, andNO1-CP-21 I15 from the U.S. National Cancer Institute.

Keywords

Carcinogenicity
Esophagus
Lung
Metabolic activation
Oral cavity
Pancreas
Synthesis
Tobacco-specific N-nitrosamines
α-hydroxylation.

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10.3109/10408449609017927

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title = "Synthesis of tobacco-specific N-nitrosamines and their metabolites and results of related bioassays",

abstract = "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.",

keywords = "Carcinogenicity, Esophagus, Lung, Metabolic activation, Oral cavity, Pancreas, Synthesis, Tobacco-specific N-nitrosamines, α-hydroxylation.",

author = "Shantu Amin and Dhimant Desai and Hecht, {Stephen S.} and Dietrich Hoffmann",

note = "Funding Information: Our studies are supported by grants CA-29580, CA-44377, andNO1-CP-21 I15 from the U.S. National Cancer Institute.",

year = "1996",

doi = "10.3109/10408449609017927",

language = "English (US)",

volume = "26",

pages = "139--147",

journal = "Critical Reviews in Toxicology",

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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.

KW - Carcinogenicity

KW - Esophagus

KW - Lung

KW - Metabolic activation

KW - Oral cavity

KW - Pancreas

KW - Synthesis

KW - Tobacco-specific N-nitrosamines

KW - α-hydroxylation.

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U2 - 10.3109/10408449609017927

DO - 10.3109/10408449609017927

M3 - Review article

C2 - 8688157

AN - SCOPUS:0029968631

SN - 1040-8444

VL - 26

SP - 139

EP - 147

JO - Critical Reviews in Toxicology

JF - Critical Reviews in Toxicology

IS - 2

ER -

Synthesis of tobacco-specific N-nitrosamines and their metabolites and results of related bioassays

Abstract

Bibliographical note

Keywords

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