Environmental Health Perspectives 105, Supplement 1, February 1997

Approaches to Chemoprevention of Lung Cancer Based on Carcinogens in Tobacco Smoke

Stephen S. Hecht

University of Minnesota Cancer Center, Minneapolis, Minnesota

Abstract
Chemoprevention may be one way to prevent lung cancer in smokers who are motivated to quit but cannot stop. The approach to chemoprevention of lung cancer described in this article is based on an understanding of the lung carcinogens present in tobacco smoke. The available data indicate that the compounds in cigarette smoke most likely involved in the induction of lung cancer in humans are the complex of polynuclear aromatic hydrocarbons typified by benzo[a]pyrene (B[a]P) and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A large number of compounds are now available that inhibit lung tumorigenesis by B[a]P or NNK in rodents. Inhibition of NNK-induced lung carcinogenesis by phenethyl isothiocyanate (PEITC) and inhibition of B[a]P-induced lung carcinogenesis by benzyl isothiocyanate (BITC) are discussed as examples. Studies with PEITC in rodents clearly demonstrate that it inhibits NNK-induced lung tumorigenesis by inhibiting the metabolic activation of NNK. Similar changes appear to occur in humans according to data generated in smokers who ate watercress, a source of PEITC. It is likely that mixtures of chemopreventive agents with activity against carcinogens in tobacco smoke, such as NNK and B[a]P, will be useful in chemoprevention of lung cancer in smokers. Furthermore, there is a need to develop suppressing agents for lung cancer that might be applicable in both smokers and ex-smokers. -- Environ Health Perspect 105(Suppl 4):955-963 (1997)

Key words: chemoprevention, tobacco smoke, benzo[a]pyrene, B[a]P, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, NNK, phenethyl isothiocyanate, PEITC

This paper is based on a presentation at the symposium on Mechanisms and Prevention of Environmentally Caused Cancers held 21-25 October 1995 in Santa Fe, New Mexico. Manuscript received at EHP 16 April 1996; accepted 12 August 1996.

Our research on chemoprevention is supported by Grant CA-46535 from the U.S. National Cancer Institute.

Address correspondence to Dr. S.S. Hecht, University of Minnesota Cancer Center, Box 806-UMHC, 420 Delaware Street SE, Minneapolis, MN 55455. Telephone: (612) 624-7604. Fax: (612) 626-5135. E-mail: hecht002@gold.tc.umn.edu

Abbreviations used: B[a]P, benzo[a]pyrene; BITC, benzyl isothiocyanate; HPB, 4-hydroxy-1-(3-pyridyl)-1-butanone; NNAL, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; NNAL-gluc, [4-(methylnitro- samino)-1-(3-pyridyl)but-1-yl]-ß-O-d-glucosiduronic acid; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; NNN, N´-nitrosonornicotine; PAHs, polynuclear aromatic hydrocarbons; PEITC, phenethyl isothiocyanate; PEITC-NAC, N-acetyl-S-(N-phenethylthiocarbamoyl)-l-cysteine.

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Last Update: June 30, 1997