A/j mouse lung tumorigenesis by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by arylalkyl isothiocyanates

Stephen S. Hecht, Mark A. Morse, Karin I. Eklind, Fung Lung Chung

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22 Scopus citations

Abstract

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen found in tobacco and tobacco smoke. It is a potent lung tumorigen in rodents and appears to be involved in human cancer induced by tobacco products. NNK induces lung tumors in A/J mice after a single dose; tumor multiplicity is higher when the mice are maintained on an AIN-76A diet than when they are maintained on NIH-07 diet. This paper reviews our recent research using this single-dose model. Bioassays of deuterium substituted analogues of NNK have demonstrated that methylation of DNA by NNK is an important step in lung tumor induction. Arylalkyl isothiocyanates inhibit the metabolic activation of NNK and consequently inhibit its DNA binding and tumorigenesis. Structure activity studies have demonstrated that increasing alkyl chain length leads to increasing efficacy in prevention of NNK tumorigenesis. Thus, 3-phenylpropyl isothiocyanate and 4-phenylbutyl isothiocyanate blocked NNK induced lung tumor formation in A/J mice. Lower doses of longer chain arylalkyl isothiocyanates were even more effective as chemopreventive agents.

Original languageEnglish (US)
Pages (from-to)501-511
Number of pages11
JournalExperimental Lung Research
Volume17
Issue number2
DOIs
StatePublished - Jan 1 1991

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