Journal ArticleDOI
Tobacco-specific N-nitrosamines and Areca-derived N-nitrosamines : chemistry, biochemistry, carcinogenicity, and relevance to humans
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TLDR
Evidence is presented that strongly supports the concept that TSNA contribute to the increased risk for cancer of the upper digestive tract in tobacco chewers and for the increase risk of lung cancer, especially pulmonary adenocarcinoma, in smokers.Abstract:
Nicotine and the minor tobacco alkaloids give rise to tobacco-specific N-nitrosamines (TSNA) during tobacco processing and during smoking. Chemical-analytical studies led to the identification of seven TSNA in smokeless tobacco (< or = 25 micrograms/g) and in mainstream smoke of cigarettes (1.3 micrograms TSNA/cigarette). Indoor air polluted by tobacco smoke may contain up to 24 pg/L of TSNA. In mice, rats, and hamsters, three TSNA, N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are powerful carcinogens; two TSNA are moderately active as carcinogens; and two TSNA appear not to be carcinogenic. The TSNA are procarcinogens, agents that require metabolic activation. The active forms of the carcinogenic TSNA react with cellular components, including DNA, and with hemoglobin (Hb). The Hb adducts in chewers and smokers serve as biomarkers for the uptake and metabolic activation of carcinogenic TSNA and the urinary excretion of NNAL as free alcohol and as glucuronide for the uptake of TSNA. The review presents evidence that strongly supports the concept that TSNA contribute to the increased risk for cancer of the upper digestive tract in tobacco chewers and for the increased risk of lung cancer, especially pulmonary adenocarcinoma, in smokers. The high incidence of cancer of the upper digestive tract especially among men on the Indian subcontinent has been causally associated with chewing of betel quid mixed with tobacco. In addition to the TSNA, the betel quid chewers are exposed to four N-nitrosamines that are formed during chewing from the Areca alkaloids, two of these N-nitrosamines are carcinogens. The article also reviews approaches toward the reduction of the carcinogenic potency of smokeless tobacco, betel quid-tobacco mixtures, and cigarette smoke. Although the safest way to reduce the risk for tobacco-related cancers is to refrain from chewing and smoking, modifications of smokeless tobacco and of cigarettes are indicated to lead to less toxic products. Another more recent approach for reducing the carcinogenic effect of tobacco products is the application of chemopreventive agents, primarily of micronutrients. Future aspects in tobacco carcinogenesis, especially as it relates to TSNA, are expected in the field of molecular biochemistry and in biomarker studies, with the goal of identifying those tobacco and betel quid chewers and tobacco smokers who are at especially high risk for cancer.read more
Citations
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Journal ArticleDOI
Impact of alleles at the Yellow Burley (Yb) loci and nitrogen fertilization rate on nitrogen utilization efficiency and tobacco-specific nitrosamine (TSNA) formation in air-cured tobacco.
Ramsey S. Lewis,Robert G Parker,David A. Danehower,Karen Andres,Anne M. Jack,D. Scott Whitley,Lowell P. Bush +6 more
TL;DR: Recessive alleles at Yb(1) and Yb (2) were associated with increased alkaloid levels, reduced nitrogen use efficiency, reducednitrogen utilization efficiency, and increased leaf nitrate nitrogen (NO(3)-N).
Journal ArticleDOI
Quantitation of pyridyloxobutyl DNA adducts in nasal and oral mucosa of rats treated chronically with enantiomers of N′-nitrosonornicotine
TL;DR: The results indicate that different mechanisms are involved in NNN metabolism and tumorigenesis in rat nasal and oral tissues, and support the potential importance of NNN as an oral carcinogen in people who use smokeless tobacco products.
Journal ArticleDOI
Tobacco Use, Insulin Resistance, and Risk of Type 2 Diabetes: Results from the Multi-Ethnic Study of Atherosclerosis.
Rachel J. Keith,Rachel J. Keith,Mahmoud Al Rifai,Mahmoud Al Rifai,Christopher Carruba,Natasha De Jarnett,Natasha De Jarnett,John W. McEvoy,Aruni Bhatnagar,Aruni Bhatnagar,Michael J. Blaha,Michael J. Blaha,Andrew P. DeFilippis +12 more
TL;DR: The role smoking plays in causing diabetes may be more complicated than originally thought and warrants more in-depth large contemporary multi-ethnic studies.
Patent
Compositions and methods for minimizing nornicotine synthesis in tobacco
Ralph E. Dewey,Ramsey S. Lewis +1 more
TL;DR: In this article, a set of polynucleotides and polypeptides for a root-specific nicotine demethylases, namely, CYP82E10, and variants thereof, were isolated polynomial structures for the demethylase gene.
Journal ArticleDOI
How Each Component of Betel Quid Is Involved in Oral Carcinogenesis: Mutual Interactions and Synergistic Effects with Other Carcinogens-a Review Article.
Shajedul Islam,Malsantha Muthumala,Hirofumi Matsuoka,Osamu Uehara,Yasuhiro Kuramitsu,Itsuo Chiba,Yoshihiro Abiko +6 more
TL;DR: Betel quid and other carcinogenic components, mainly contribute to downregulate the antioxidant proteins and lead to the induction of ROS, and the elimination of ROS may prove most effective chemoprevention for betel qud-mediated oral carcinogenesis.
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TL;DR: ImagesFigs.