Tobacco-specific nitrosamines, an important group of carcinogens in tobacco and tobacco smoke

Abstract

Tobacco-specific nitrosamines are a group of carcinogens that are present in tobacco and tobacco smoke. They are formed from nicotine and related tobacco alkaloids. Two of the nicotine-derived nitrosamines, NNK and NNN, are strong carcinogens in laboratory animals. They can induce tumors both locally and systemically. The induction of oral cavity tumors by a mixture of NNK and NNN, and the organospecificity of NNK for the lung are particularly noteworthy. The amounts of NNK and NNN in tobacco and tobacco smoke are high enough that their total estimated doses to long-term snuff-dippers or smokers are similar in magnitude to the total doses required to produce cancer in laboratory animals. These exposures thus represent an unacceptable risk to tobacco consumers, and possibly to non-smokers exposed for years to environmental tobacco smoke. The permission of such high levels of carcinogens in consumer products used by millions of people represents a major legislative failure. Indeed, the levels of tobacco-specific nitrosamines in tobacco are thousands of times higher than the amounts of other nitrosamines in consumer products that are regulated by government authorities. Although the role of tobacco-specific nitrosamines as causative factors in tobacco-related human cancers cannot be assessed with certainty because of the complexity of tobacco and tobacco smoke, several lines of evidence strongly indicate that they have a major role, especially in the causation of oral cancer in snuff-dippers. Epidemiologic studies have demonstrated that snuff-dipping causes oral cancer. NNK and NNN are quantitatively the most prevalent known carcinogens in snuff, and they induce oral tumors when applied to the rat oral cavity. A role for NNK in the induction of lung cancer by tobacco smoke is likely because of its organospecificity for the lung. Tobacco-specific nitrosamines may also be involved in the etiology of tobacco-related cancers of the esophagus, nasal cavity, and pancreas. Because they are derived from nicotine, and therefore should be associated only with tobacco, tobacco smoke and other nicotine-containing products, tobacco-specific nitrosamines as well as their metabolites and macromolecular adducts should be ideal markers for assessing human exposure to, and metabolic activation of, tobacco smoke carcinogens. Ongoing research has demonstrated the formation of globin and DNA adducts of NNK and NNN in experimental animals. Sensitive methods for the detection and quantitation of these adducts in humans would provide an approach to assessing individual risk for tobacco-related cancers.(ABSTRACT TRUNCATED AT 400 WORDS)

Case‐control study evaluating the homogeneity and heterogeneity of risk factors between sinonasal and nasopharyngeal cancers

“…9 Such associations are rational because all sites within the respiratory system are directly exposed to tobacco smoke, which can generate many carcinogens such as tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, aromatic amines, aldehydes, phenol, catechol and some free radicals. 9,10 Previous studies have demonstrated that smokers have increased risk of developing cancers of the nasal cavity and paranasal sinus, especially those with squamous cell histologic type. [11][12][13][14] Although less consistent, studies also have shown a positive association between cigarette smoking and nasopharyngeal cancer, 15,16 especially in low risk areas.…”

Identification of Adducts Formed in the Reaction of 5‘-Acetoxy-N‘-Nitrosonornicotine with Deoxyguanosine and DNA

“…Hydroxy acid 34 was allowed to react with acidic methanol followed by (S)-(−)-α-methylbenzyl isocyanate to give methyl 4-[α-methylbenzylcarbamoyl]-4-(3-pyridyl)butanoate (MMPB, 35) as described (22,23). The mixture was purified with HPLC system 4, and LC-ESI-MS and HPLC-UV analysis were carried out using system 5, except that there was a hold at 60% CH 3 …”

“…Nicotine is the principal known addictive agent in tobacco products and is the reason why most people cannot break their tobacco habit in spite of a strong desire to quit (1). Nicotine is not carcinogenic, but replacement of its methyl group by a nitroso-group produces the carcinogen NNN (2)(3)(4). NNN, which is present in both unburned tobacco and tobacco smoke, causes tumors of the esophagus and nasal cavity in rats, and the respiratory tract in mice, hamsters, and mink (2)(3)(4).…”

Tobacco‐specific nitrosamines in smokeless tobacco products marketed in India

“…[5][6][7][8][9][10][11] These carcinogens are formed from tobacco alkaloids during the curing and processing of tobacco. Vast amounts of data convincingly demonstrate their presence in various forms of smokeless tobacco, but products available in India have been examined in only scattered studies and there have been no reports since 1989.…”

“…Vast amounts of data convincingly demonstrate their presence in various forms of smokeless tobacco, but products available in India have been examined in only scattered studies and there have been no reports since 1989. 6,[12][13][14][15][16][17] In view of the variety of new smokeless tobacco products now available in India and the widespread use of these products, it is important to obtain current data on levels of tobacco-specific nitrosamines. Such data are critical in approaches to the control and regulation of smokeless tobacco products in India, and ultimately to prevention of oral cancer.…”