Effects of alkyl chain length on the inhibition of nnk-induced lung neoplasia in a/j mice by arylalkyl isothiocyanates

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

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Abstract

Six homologous arylalkyl isothiocyanates were evaluated for their abilities to inhibit pulmonary adenomas induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-l-(3-pyridyl)-1-butanone (NNK) in A/J mice. Four consecutive daily doses (5 μmol/mouse) of phenyl isothiocyanate (PITC), benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PETTC), 3-phenylpropyl isothiocyanate (PPITC), 4-phenylbutyl isothiocyanate (PBITC), 4-oxo-4-(3-pyridyl)-butyl isothiocyanate (OPBITC) and corn ofl were administered to mice by gavage. Two hours following the final dosing, mice were administered saline or 10 μmol of NNK in saline i.p. Pulmonary adenomas were counted at 16 weeks after NNK administration. The mice administered only corn oil prior to NNK developed an average multiplicity of 9.2 tumors/ mouse. Pretreatment with PITC, BITC and OPBITC had no significant effects on NNK-induced lung neoplasia. However, PEITC pretreatment resulted in a 64% reduction of lung tumor multiplicity, but did not affect the percentage of mice that developed tumors. Both PPITC and PBITC decreased tumor multiplicity by 96% and the percentage of tumor-bearing animals by >60%. These results, in conjunction with our previous work, demonstrate a general trend of increasing inhibition of NNK-induced lung neoplasia by arylalkyl isothiocyanates with increasing alkyl chain length. This study also demonstrates the remarkable inhibitory activities of PPITC and PBITC, two isothiocyanates that had not previously been tested as chemopreventive agents.

Original languageEnglish (US)
Pages (from-to)1757-1759
Number of pages3
JournalCarcinogenesis
Volume10
Issue number9
DOIs
StatePublished - Sep 1989

Bibliographical note

Funding Information:
The authors wish to thank Kevin Jordan, Joanne Braley, Patricia Little and Chang-In Choi for their invaluable contributions in performing the A/J pulmonary adenoma assays. We also thank Mark Kagan for performing mass spectrometry and Dr Bijaya Misra for providing us with NMR data. This study was supported by National Cancer Institute Grant CA-46535. This paper is no. 6 in 'Dietary inhibitors of chemical carcinogenesis'.

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