From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications

Autores: Stanfill, Stephen B.; Hecht, Stephen S.; Joerger, Andreas C.; González, Pablo Javier; Maia, Luisa B.; Rivas, Maria Gabriela; Moura, José J. G.; Gupta, Alpana K.; Le Brun, Nick E.; Crack, Jason C.; Hainaut, Pierre; Sparacino Watkins, Courtney; Tyx, Robert E.; Pillai, Suresh D.; Zaatari, Ghazi S.; Henley, S. Jane; Blount, Benjamin C.; Watson, Clifford H.; Kaina, Bernd; Mehrotra, Ravi
Año de publicación: 2023
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N′-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.
Fil: Stanfill, Stephen B.. National Center For Environmental Health; Estados Unidos
Fil: Hecht, Stephen S.. University of Minnesota; Estados Unidos
Fil: Joerger, Andreas C.. Goethe Universitat Frankfurt; Alemania
Fil: González, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; Argentina
Fil: Maia, Luisa B.. Universidade Nova de Lisboa; Portugal
Fil: Rivas, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; Argentina
Fil: Moura, José J. G.. Universidade Nova de Lisboa; Portugal
Fil: Gupta, Alpana K.. Independent Research Consultant; India
Fil: Le Brun, Nick E.. University of East Anglia; Reino Unido
Fil: Crack, Jason C.. University of East Anglia; Reino Unido
Fil: Hainaut, Pierre. Universite Grenoble Alpes; Francia
Fil: Sparacino Watkins, Courtney. Univeristy of Pittsburgh. School of Medicine; Estados Unidos. Vascular Medicine Institute; Estados Unidos
Fil: Tyx, Robert E.. National Center For Environmental Health; Estados Unidos
Fil: Pillai, Suresh D.. Texas A&M University; Estados Unidos
Fil: Zaatari, Ghazi S.. American University Of Beirut; Líbano
Fil: Henley, S. Jane. Centers for Disease Control and Prevention; Estados Unidos
Fil: Blount, Benjamin C.. National Center For Environmental Health; Estados Unidos
Fil: Watson, Clifford H.. National Center For Environmental Health; Estados Unidos
Fil: Kaina, Bernd. University Medical Center; Alemania
Fil: Mehrotra, Ravi. Innovation And Policy Foundation; India
Materia: CANCER
DISSIMILATORY NITRATE REDUCTASE
DNA REPAIR
MUTAGENICITY
MUTATION
NITRATE-REDUCING BACTERIA
NNK
NNN
ONCOGENE
P53
RAS
SMOKELESS TOBACCO
TOBACCO-SPECIFIC N-NITROSAMINES
TSNA
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/publicdomain/zero/1.0/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/227549

Acceder

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network_acronym_str	CONICETDig
repository_id_str	3498
network_name_str	CONICET Digital (CONICET)
spelling	From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implicationsStanfill, Stephen B.Hecht, Stephen S.Joerger, Andreas C.González, Pablo JavierMaia, Luisa B.Rivas, Maria GabrielaMoura, José J. G.Gupta, Alpana K.Le Brun, Nick E.Crack, Jason C.Hainaut, PierreSparacino Watkins, CourtneyTyx, Robert E.Pillai, Suresh D.Zaatari, Ghazi S.Henley, S. JaneBlount, Benjamin C.Watson, Clifford H.Kaina, BerndMehrotra, RaviCANCERDISSIMILATORY NITRATE REDUCTASEDNA REPAIRMUTAGENICITYMUTATIONNITRATE-REDUCING BACTERIANNKNNNONCOGENEP53RASSMOKELESS TOBACCOTOBACCO-SPECIFIC N-NITROSAMINESTSNAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N′-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.Fil: Stanfill, Stephen B.. National Center For Environmental Health; Estados UnidosFil: Hecht, Stephen S.. University of Minnesota; Estados UnidosFil: Joerger, Andreas C.. Goethe Universitat Frankfurt; AlemaniaFil: González, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; ArgentinaFil: Maia, Luisa B.. Universidade Nova de Lisboa; PortugalFil: Rivas, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; ArgentinaFil: Moura, José J. G.. Universidade Nova de Lisboa; PortugalFil: Gupta, Alpana K.. Independent Research Consultant; IndiaFil: Le Brun, Nick E.. University of East Anglia; Reino UnidoFil: Crack, Jason C.. University of East Anglia; Reino UnidoFil: Hainaut, Pierre. Universite Grenoble Alpes; FranciaFil: Sparacino Watkins, Courtney. Univeristy of Pittsburgh. School of Medicine; Estados Unidos. Vascular Medicine Institute; Estados UnidosFil: Tyx, Robert E.. National Center For Environmental Health; Estados UnidosFil: Pillai, Suresh D.. Texas A&M University; Estados UnidosFil: Zaatari, Ghazi S.. American University Of Beirut; LíbanoFil: Henley, S. Jane. Centers for Disease Control and Prevention; Estados UnidosFil: Blount, Benjamin C.. National Center For Environmental Health; Estados UnidosFil: Watson, Clifford H.. National Center For Environmental Health; Estados UnidosFil: Kaina, Bernd. University Medical Center; AlemaniaFil: Mehrotra, Ravi. Innovation And Policy Foundation; IndiaTaylor & Francis2023-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/227549Stanfill, Stephen B.; Hecht, Stephen S.; Joerger, Andreas C.; González, Pablo Javier; Maia, Luisa B.; et al.; From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications; Taylor & Francis; Critical Reviews In Toxicology; 53; 10; 11-2023; 658-7011040-8444CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/10408444.2023.2264327info:eu-repo/semantics/altIdentifier/doi/10.1080/10408444.2023.2264327info:eu-repo/semantics/openAccesshttps://creativecommons.org/publicdomain/zero/1.0/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T15:08:18Zoai:ri.conicet.gov.ar:11336/227549instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-08-25 15:08:18.69CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications
title	From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications
spellingShingle	From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications Stanfill, Stephen B. CANCER DISSIMILATORY NITRATE REDUCTASE DNA REPAIR MUTAGENICITY MUTATION NITRATE-REDUCING BACTERIA NNK NNN ONCOGENE P53 RAS SMOKELESS TOBACCO TOBACCO-SPECIFIC N-NITROSAMINES TSNA
title_short	From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications
title_full	From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications
title_fullStr	From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications
title_full_unstemmed	From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications
title_sort	From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications
dc.creator.none.fl_str_mv	Stanfill, Stephen B. Hecht, Stephen S. Joerger, Andreas C. González, Pablo Javier Maia, Luisa B. Rivas, Maria Gabriela Moura, José J. G. Gupta, Alpana K. Le Brun, Nick E. Crack, Jason C. Hainaut, Pierre Sparacino Watkins, Courtney Tyx, Robert E. Pillai, Suresh D. Zaatari, Ghazi S. Henley, S. Jane Blount, Benjamin C. Watson, Clifford H. Kaina, Bernd Mehrotra, Ravi
author	Stanfill, Stephen B.
author_facet	Stanfill, Stephen B. Hecht, Stephen S. Joerger, Andreas C. González, Pablo Javier Maia, Luisa B. Rivas, Maria Gabriela Moura, José J. G. Gupta, Alpana K. Le Brun, Nick E. Crack, Jason C. Hainaut, Pierre Sparacino Watkins, Courtney Tyx, Robert E. Pillai, Suresh D. Zaatari, Ghazi S. Henley, S. Jane Blount, Benjamin C. Watson, Clifford H. Kaina, Bernd Mehrotra, Ravi
author_role	author
author2	Hecht, Stephen S. Joerger, Andreas C. González, Pablo Javier Maia, Luisa B. Rivas, Maria Gabriela Moura, José J. G. Gupta, Alpana K. Le Brun, Nick E. Crack, Jason C. Hainaut, Pierre Sparacino Watkins, Courtney Tyx, Robert E. Pillai, Suresh D. Zaatari, Ghazi S. Henley, S. Jane Blount, Benjamin C. Watson, Clifford H. Kaina, Bernd Mehrotra, Ravi
author2_role	author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	CANCER DISSIMILATORY NITRATE REDUCTASE DNA REPAIR MUTAGENICITY MUTATION NITRATE-REDUCING BACTERIA NNK NNN ONCOGENE P53 RAS SMOKELESS TOBACCO TOBACCO-SPECIFIC N-NITROSAMINES TSNA
topic	CANCER DISSIMILATORY NITRATE REDUCTASE DNA REPAIR MUTAGENICITY MUTATION NITRATE-REDUCING BACTERIA NNK NNN ONCOGENE P53 RAS SMOKELESS TOBACCO TOBACCO-SPECIFIC N-NITROSAMINES TSNA
purl_subject.fl_str_mv	https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv	Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N′-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients. Fil: Stanfill, Stephen B.. National Center For Environmental Health; Estados Unidos Fil: Hecht, Stephen S.. University of Minnesota; Estados Unidos Fil: Joerger, Andreas C.. Goethe Universitat Frankfurt; Alemania Fil: González, Pablo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; Argentina Fil: Maia, Luisa B.. Universidade Nova de Lisboa; Portugal Fil: Rivas, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; Argentina Fil: Moura, José J. G.. Universidade Nova de Lisboa; Portugal Fil: Gupta, Alpana K.. Independent Research Consultant; India Fil: Le Brun, Nick E.. University of East Anglia; Reino Unido Fil: Crack, Jason C.. University of East Anglia; Reino Unido Fil: Hainaut, Pierre. Universite Grenoble Alpes; Francia Fil: Sparacino Watkins, Courtney. Univeristy of Pittsburgh. School of Medicine; Estados Unidos. Vascular Medicine Institute; Estados Unidos Fil: Tyx, Robert E.. National Center For Environmental Health; Estados Unidos Fil: Pillai, Suresh D.. Texas A&M University; Estados Unidos Fil: Zaatari, Ghazi S.. American University Of Beirut; Líbano Fil: Henley, S. Jane. Centers for Disease Control and Prevention; Estados Unidos Fil: Blount, Benjamin C.. National Center For Environmental Health; Estados Unidos Fil: Watson, Clifford H.. National Center For Environmental Health; Estados Unidos Fil: Kaina, Bernd. University Medical Center; Alemania Fil: Mehrotra, Ravi. Innovation And Policy Foundation; India
description	Tobacco use is a major cause of preventable morbidity and mortality globally. Tobacco products, including smokeless tobacco (ST), generally contain tobacco-specific N-nitrosamines (TSNAs), such as N′-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK), which are potent carcinogens that cause mutations in critical genes in human DNA. This review covers the series of biochemical and chemical transformations, related to TSNAs, leading from tobacco cultivation to cancer initiation. A key aim of this review is to provide a greater understanding of TSNAs: their precursors, the microbial and chemical mechanisms that contribute to their formation in ST, their mutagenicity leading to cancer due to ST use, and potential means of lowering TSNA levels in tobacco products. TSNAs are not present in harvested tobacco but can form due to nitrosating agents reacting with tobacco alkaloids present in tobacco during certain types of curing. TSNAs can also form during or following ST production when certain microorganisms perform nitrate metabolism, with dissimilatory nitrate reductases converting nitrate to nitrite that is then released into tobacco and reacts chemically with tobacco alkaloids. When ST usage occurs, TSNAs are absorbed and metabolized to reactive compounds that form DNA adducts leading to mutations in critical target genes, including the RAS oncogenes and the p53 tumor suppressor gene. DNA repair mechanisms remove most adducts induced by carcinogens, thus preventing many but not all mutations. Lastly, because TSNAs and other agents cause cancer, previously documented strategies for lowering their levels in ST products are discussed, including using tobacco with lower nornicotine levels, pasteurization and other means of eliminating microorganisms, omitting fermentation and fire-curing, refrigerating ST products, and including nitrite scavenging chemicals as ST ingredients.
publishDate	2023
dc.date.none.fl_str_mv	2023-11
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/11336/227549 Stanfill, Stephen B.; Hecht, Stephen S.; Joerger, Andreas C.; González, Pablo Javier; Maia, Luisa B.; et al.; From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications; Taylor & Francis; Critical Reviews In Toxicology; 53; 10; 11-2023; 658-701 1040-8444 CONICET Digital CONICET
url	http://hdl.handle.net/11336/227549
identifier_str_mv	Stanfill, Stephen B.; Hecht, Stephen S.; Joerger, Andreas C.; González, Pablo Javier; Maia, Luisa B.; et al.; From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications; Taylor & Francis; Critical Reviews In Toxicology; 53; 10; 11-2023; 658-701 1040-8444 CONICET Digital CONICET
dc.language.none.fl_str_mv	eng
language	eng
dc.relation.none.fl_str_mv	info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1080/10408444.2023.2264327 info:eu-repo/semantics/altIdentifier/doi/10.1080/10408444.2023.2264327
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dc.publisher.none.fl_str_mv	Taylor & Francis
publisher.none.fl_str_mv	Taylor & Francis
dc.source.none.fl_str_mv	reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas
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repository.mail.fl_str_mv	dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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From cultivation to cancer: Formation of N-nitrosamines and other carcinogens in smokeless tobacco and their mutagenic implications

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