The Biological Significance of Tobacco-SpecificN-Nitrosamines: Smoking and Adenocarcinoma of the Lung

Abstract

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.

Key Words:

• tobacco-specificN-nitrosamines (TSNA)
• lung adenocarcinoma (AC)
• 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
• metabolic activation
• K-ras oncogene activation
• SCC
• squamous cell carcinoma