Journal ArticleDOI
Tobacco-specific N-nitrosamines and Areca-derived N-nitrosamines : chemistry, biochemistry, carcinogenicity, and relevance to humans
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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
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References
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N'-nitrosonornicotine in tobacco.
TL;DR: N'-Nitrosonornicotine, a potential carcinogen, has been positively identified in unburned tobacco and is the first example of a potential organic carcinogen isolated from tobacco.
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Significant changes in the distribution of histologic types of lung cancer. A review of 4928 cases
TL;DR: The analysis of histopathologic data for lung carcinoma indicates that lung cancer is increasing in the authors' region, and small cell carcinoma has increased over the past years and may become the most common type of lung cancer in women.
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Association of Dietary Fat and Lung Cancer
TL;DR: An international comparison study of the relationship among dietary predictors, tobacco consumption, income, and truncated age-adjusted lung cancer mortality was conducted with the use of time-lagged data available for 43 countries showed that calories from dietary fat were highly significantly associated with lungcancer mortality.
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Metabolism of tobacco-specific N-nitrosamines by cultured human tissues
TL;DR: The results of the present study demonstrate that explants of these tissues as well as of the urinary bladder have the capacity to metabolize NNN and NNK by alpha-carbon hydroxylation, further evidence that tobacco-specific N-nitrosamines could play a role in cancers related to the smoking and chewing of tobacco.
Journal ArticleDOI
Reaction of Nitrite With Ascorbate and Its Relation to Nitrosamine Formation
TL;DR: A pH- dependent induction period observed during the nitrosation of morpholine in the presence of ascorbate and excess nitrite was accounted for by the kinetics of the reactions.