Cigarette smoking and adenocarcinoma of the lung: The relevance of nicotine-derived N-nitrosamines

D. Hoffmann, A. Rivenson, S. E. Murphy, F. L. Chung, S. Amin, S. S. Hecht

Research output: Contribution to journalReview articlepeer-review

62 Scopus citations


The incidence of pulmonary adenocarcinoma has increased significantly more than squamous cell carcinoma among male cigarette smokers in a number of developed countries. In part, this significant difference is likely due to the consumer acceptance of low-tar, low-nicotine cigarettes which are smoked by drawing puffs more frequently and by taking larger puffs than in high-yield cigarettes. One change in the composition of low tar cigarettes is an increase of the nitrate content and, since nitrate is an important precursor of N-nitrosamines formed during tobacco processing and smoking, the yield of carcinogenic, tobacco-specific N-nitrosamines (TSNA) in the smoke has therefore increased. The nicotine-derived TSNA, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), specifically induces pulmonary adenoma and adenocarcinoma in laboratory rodents and the lowest dose required to induce lung tumours in rats compares well with the dose of NNK inhaled by a long-term cigarette smoker. NNK is a pro-carcinogen which requires metabolic activation and this occurs in rodent, as well as in human, tissue primarily by α-hydroxylation. The DNA-adducts so formed are mutagenic lesions which activate oncogenes. The above cited observations support the concept that TSNA, and especially NNK play an important role in the induction of adenocarcinoma of cigarette smokers. Although abstaining from smoking is the only certain way to avoid tobacco-related diseases, including lung cancer, two approaches are discussed for reducing the risk of smoking-related diseases in those smokers who are not willing to give up their tobacco habit. One lies in reducing the toxicity and carcinogenicity of the smoke by reducing the nitrate content of the tobacco. Another is through the use of chemopreventive agents that inhibit the development of lung cancer. Both of these concepts are reviewed and studies strengthening the working hypothesis that NNK plays an important role in the association of cigarette smoking with pulmonary adenocarcinoma are discussed.

Original languageEnglish (US)
Pages (from-to)165-189
Number of pages25
JournalJournal of Smoking-Related Disorders
Issue number3
StatePublished - 1993

All Science Journal Classification (ASJC) codes

  • General Medicine


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