| Autor: |
Stanfill SB; Tobacco and Volatiles Branch, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA., Hecht SS; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA., Joerger AC; Structural Genomics Consortium (SGC), Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt am Main, Germany., González PJ; Department of Physics, Universidad Nacional Litoral, and CONICET, Santa Fe, Argentina., Maia LB; Department of Chemistry, LAQV, REQUIMTE, NOVA School of Science and Technology (FCT NOVA), Caparica, Portugal., Rivas MG; Department of Physics, Universidad Nacional Litoral, and CONICET, Santa Fe, Argentina., Moura JJG; Department of Chemistry, LAQV, REQUIMTE, NOVA School of Science and Technology (FCT NOVA), Caparica, Portugal., Gupta AK; Independent Research Consultant (Cancer), Noida, India., Le Brun NE; School of Chemistry, Centre for Molecular and Structural Biochemistry, University of East Anglia, Norwich, UK., Crack JC; School of Chemistry, Centre for Molecular and Structural Biochemistry, University of East Anglia, Norwich, UK., Hainaut P; Institute for Advanced Biosciences, Grenoble Alpes University, Grenoble, France., Sparacino-Watkins C; University of Pittsburgh, School of Medicine, Division of Pulmonary Allergy and Critical Care Medicine, Vascular Medicine Institute, PA, USA., Tyx RE; Tobacco and Volatiles Branch, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA., Pillai SD; Department of Food Science & Technology, National Center for Electron Beam Research, Texas A&M University, College Station, TX, USA., Zaatari GS; Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon., Henley SJ; Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA., Blount BC; Tobacco and Volatiles Branch, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA., Watson CH; Tobacco and Volatiles Branch, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA., Kaina B; Institute of Toxicology, University Medical Center, Mainz, Germany., Mehrotra R; Centre for Health, Innovation and Policy Foundation, Noida, India. |
| Abstrakt: |
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. |
