TOBACCO-SPECIFIC NITROSAMINES, AN IMPORTANT GROUP OF CARCINOGENS IN TOBACCO AND TOBACCO-SMOKE
TOBACCO-SPECIFIC NITROSAMINES, AN IMPORTANT GROUP OF CARCINOGENS IN TOBACCO AND TOBACCO-SMOKE
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DOI：
10.1093/carcin/9.6.875
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发表时间：
1988-06-01
期刊：
影响因子：
4.7
通讯作者：
HOFFMANN, D
中科院分区：
文献类型：
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作者：
HECHT, SS;HOFFMANN, D
烟草特有的亚硝胺是一组存在于烟草和烟草烟雾中的致癌物质。它们由尼古丁和相关的烟草生物碱形成。尼古丁衍生的亚硝胺中的两种，NNK和NNN，在实验室动物中是强致癌物。它们可以在局部和全身诱发肿瘤。NNK和NNN的混合物对口腔肿瘤的诱导以及NNK对肺的器官特异性特别值得注意。烟草和烟草烟雾中NNK和NNN的含量足够高，以至于长期吸鼻烟者或吸烟者的总估计剂量与实验室动物产生癌症所需的总剂量相似。因此，这些暴露对烟草消费者以及可能对多年暴露于环境烟草烟雾的非吸烟者来说是不可接受的风险。允许数百万人使用的消费品中含有如此高水平的致癌物是一个重大的立法失败。事实上，烟草中烟草特有的亚硝胺含量比政府当局监管的消费品中其他亚硝胺含量高出数千倍。尽管由于烟草和烟草烟雾的复杂性，烟草特有的亚硝胺作为烟草相关人类癌症的致病因素的作用不能确定地评估，但几条证据强烈表明它们具有重要作用，特别是在鼻烟勺口腔癌的病因中。流行病学研究表明，鼻烟蘸会导致口腔癌。NNK和NNN在数量上是鼻烟中最普遍的已知致癌物，当应用于大鼠口腔时，它们诱导口腔肿瘤。NNK在烟草烟雾诱导肺癌中的作用可能是因为其对肺的器官特异性。烟草特有的亚硝胺也可能与烟草相关的食道癌、鼻腔癌和胰腺癌的病因有关。由于它们来自尼古丁，因此应仅与烟草、烟草烟雾和其他含尼古丁产品相关，因此烟草特异性亚硝胺及其代谢物和大分子加合物应是评估人类暴露于烟草烟雾致癌物及其代谢活化的理想标志物。正在进行的研究已经证明了在实验动物中NNK和NNN的珠蛋白和DNA加合物的形成。检测和定量人体中这些加合物的灵敏方法将提供一种评估烟草相关癌症个体风险的方法。（400字处截断摘要）
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)