Nilsson R
Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Stockholm, S-10691, Sweden.
Regul Toxicol Pharmacol. 1998 Aug;28(1):1-16. doi: 10.1006/rtph.1998.1229.
The presence of highly carcinogenic tobacco-specific nitrosamines (TSNA) in snuff has been a matter of serious concern. However, the levels of TSNA in such products may differ by orders of magnitude depending on origin and manner of processing, and the mere presence of such agents at low levels does hardly constitute a meaningful prerequisite for classifying all types of snuff as human carcinogens. Reviewing available epidemiological evidence, a wide discrepancy is found for estimated cancer risk associated with snuff dipping derived from on one hand previous investigations conducted in the United States and on the other from recent extensive Swedish epidemiological studies. In spite of the fact that approximately 20% of all grown-up Swedish males use moist snuff, it has not been possible to detect any significant increase in the incidence of cancer of the oral cavity or pharynx-the prevalence of which by international standards remains low in this country. Further, there is insufficient evidence for a causal link between the use of Swedish snuff and increased risk for cardiovascular disease. Dissimilarities in the content of TSNA in oral snuff products may represent one important reason for the different outcomes of the epidemiological surveys conducted in the United States and Sweden. Bioassays using pure TSNA in rodents appear to give exaggerated risk estimates for humans, a discrepancy that could be ascribed to species-related differences in the relation between exposure and DNA target dose and/or adduct repair rates, as well as to the presence of anticarcinogens in snuff. Although a small risk cannot be excluded, the use of smokeless tobacco products low in TSNA which now are available on the market entails a risk that at any rate is more than 10 times lower than that associated with active smoking. Nevertheless, due to the decisive role of potent TSNA in determining possible cancer risks in users of smokeless tobacco, and due to the fact that large variations in the concentrations may occur, adequate control measures should be taken to keep the levels of these nitrosamines in smokeless tobacco products as low as is technically feasible.
鼻烟中存在高致癌性的烟草特有亚硝胺(TSNA)一直是人们严重关注的问题。然而,此类产品中TSNA的含量可能因产地和加工方式而相差几个数量级,而且此类物质仅以低水平存在很难构成将所有类型鼻烟归类为人类致癌物的有意义的前提条件。回顾现有的流行病学证据,一方面在美国进行的先前调查与另一方面瑞典最近的广泛流行病学研究得出的与鼻烟蘸吸相关的估计癌症风险存在很大差异。尽管瑞典所有成年男性中约有20%使用湿鼻烟,但仍无法检测到口腔或咽癌发病率有任何显著增加——按照国际标准,该国此类癌症的患病率仍然较低。此外,没有足够证据表明使用瑞典鼻烟与心血管疾病风险增加之间存在因果关系。口腔鼻烟产品中TSNA含量的差异可能是美国和瑞典进行的流行病学调查结果不同的一个重要原因。在啮齿动物中使用纯TSNA进行的生物测定似乎对人类的风险估计过高,这种差异可归因于暴露与DNA靶剂量和/或加合物修复率之间关系的物种相关差异,以及鼻烟中存在抗癌物质。尽管不能排除存在小风险,但目前市场上可买到的TSNA含量低的无烟烟草产品带来的风险无论如何都比主动吸烟带来的风险低10倍以上。然而,由于强效TSNA在确定无烟烟草使用者可能的癌症风险中起决定性作用,而且由于浓度可能出现很大变化,应采取适当的控制措施,使无烟烟草产品中这些亚硝胺的含量在技术可行的情况下尽可能低。