The biological significance of tobacco-specific N-nitrosamines: Smoking and adenocarcinoma of the lung

Dietrich Hoffmann, Abraham Rivenson, Stephen S. Hecht

Research output: Contribution to journalReview articlepeer-review

108 Scopus citations


In the U.S., there has been a steeper rise of the incidence of lung adenocarcinoma than of squamous cell carcinoma of the lung among cigarette smokers. Since 1950, the percentage of all cigarettes sold that had filter tips increased from 0.56 to 92% in 1980 and to 97% in 1990. The tobacco of the filter cigarettes is richer in nitrate than that of the nonfilter cigarettes manufactured in past decades. Because the smoker of cigarettes with lower nicotine yield tends to smoke more intensely and to inhale the smoke more deeply than the smoker of plain cigarettes, the peripheral lung is exposed to higher amounts of nitrogen oxides, nitrosated compounds, and lung-specific smoke carcinogens. It is our working hypothesis that more intense smoking, deeper inhalation of the smoke, and higher smoke delivery of the organ-specific lung carcinogen NNK to the peripheral lung are major contributors to the increased risk of cigarette smokers for lung adenocarcinoma. Bioassay data and biochemical studies in support of this concept are discussed.

Original languageEnglish (US)
Pages (from-to)199-211
Number of pages13
JournalCritical Reviews in Toxicology
Issue number2
StatePublished - 1996

Bibliographical note

Funding Information:
We appreciate the editorial assistance of Ilse Hoffmann and Jennifer Johnting. Our studies are supported by Grants No. CA-29850 and CA-44377 and by the Cancer Center Grant No. CA-17613 from the National Cancer Institute.


  • (NNK)
  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
  • K-ras oncogene activation
  • Lung adenocarcinoma (AC)
  • Metabolic activation
  • SCC
  • Squamous cell carcinoma
  • Tobacco-specific N-nitrosamines (TSNA)


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