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
Anatomical subsite discrepancy in relation to the impact of the consumption of alcohol, tobacco and betel quid on esophageal cancer.
Chien-Hung Lee,Deng-Chyang Wu,Jang-Ming Lee,I-Chen Wu,Yih-Gang Goan,Ein-Long Kao,Hsiao-Ling Huang,Te-Fu Chan,Shah-Hwa Chou,Yi-Pin Chou,Chi-Kung Ho,Ming-Tsang Wu,Ming-Tsang Wu +12 more
TL;DR: Alcohol interacts with tobacco in a stronger supra‐multiplicative way in the middle portion of the esophagus, probably explaining why esophageal SCC occurs more commonly at this anatomical location.
Journal ArticleDOI
Identification of a prevalent functional missense polymorphism in the UGT2B10 gene and its association with UGT2B10 inactivation against tobacco-specific nitrosamines.
TL;DR: A novel polymorphism resulting in an aspartic acid to tyrosine amino acid change at codon 67 of the UGT2B10 complementary DNA was identified exclusively in subjects with a haplotype C, which may be responsible for inter individual variation in NNAL-N-glucuronidation activity and may increase susceptibility to smoking-related cancers.
Journal ArticleDOI
Alcohol and smoking in relation to the prevalence of adenomatous colorectal polyps detected at sigmoidoscopy.
Matthew P. Longnecker,Miao-Jung Chen,Nicole Probst-Hensch,Janice M. Harper,Eric R. Lee,Harold D. Frankl,Robert W. Haile +6 more
TL;DR: The hypothesis that past smoking increases the risk of large polyps is not supported, but the results indicate a weak association between alcohol use and risk of adenomatous polyps.
Journal ArticleDOI
Automated in-tube solid-phase microextraction coupled with HPLC for the determination of N-nitrosamines in cell cultures.
TL;DR: An automated in-tube solid-phase microextraction (SPME) HPLC analysis method for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and several metabolites has been developed, simplifying the determination of the TSNA.
Journal ArticleDOI
Chemical profile of two types of oral snuff tobacco.
K.D Brunnemann,J Qi,D Hoffmann +2 more
TL;DR: These two snuff brands are currently being assayed with rats in a short-term and in long-term bioassays to test the concept that the tobacco-specific N-nitrosamines are major contributors to the carcinogenic activity of oral snuff.
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TL;DR: ImagesFigs.