Effects of phenethyl isothiocyanate and benzyl isothiocyanate, individually and in combination, on lung tumorigenesis induced in A/J mice by benzo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone

Stephen S Hecht, Patrick M.J. Kenney, Mingyao Wang, Neil Trushin, Pramod Upadhyaya

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Abstract

Phenethyl isothiocyanate (PEITC) is an effective inhibitor of lung tumorigenesis induced in rats and mice by the tobacco-specific carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) while benzyl isothiocyanate (BITC) inhibits lung tumorigenesis induced in mice by another tobacco smoke carcinogen, benzo[a]pyrene (BaP). However, little is known about the inhibitory effects of PEITC and BITC in combination, or about the effects of PEITC or BITC on tumorigenesis by a mixture of NNK and BaP. In this study, we carried out a series of experiments pertinent to these questions. In Experiment 1, treatment of A/J mice with PEITC (6 μmol), BITC (6 μmol), or a combination of the two (6 μmol each) by gavage, 2 h prior to each of eight weekly gavage treatments with a mixture of BaP and NNK (3 μmol of each), had no effect on lung tumor multiplicity. In Experiment 2, we evaluated the inhibitory potential of four different mixtures of PEITC and BITC, administered by gavage 2 h prior to each of eight weekly doses of BaP and NNK, as given in Experiment 1. Mixtures of PEITC and BITC (12 μmol of each, or 12 μmol PEITC and 9 μmol BITC) significantly reduced lung tumorigenesis induced by a mixture of BaP and NNK. In Experiment 3, we investigated the effects of dietary PEITC (3 μmol/g diet), BITC (1 μmol/g diet), or a mixture of PEITC (3 μmol/g diet) and BITC (1 μmol/g diet). These compounds were started 1 week before, and continued through to 1 week after the eight weekly treatments with BaP and NNK. PEITC, and PEITC plus BITC, both significantly inhibited lung tumor multiplicity; inhibition was due mainly to PEITC. In Experiment 4, we tested dietary PEITC (3, 1, or 0.3 μmol/g diet) as an inhibitor of lung tumorigenesis induced by BaP, NNK, or BaP plus NNK using a protocol identical to that in Experiment 3. PEITC was an effective inhibitor of lung tumor multiplicity induced by NNK and a mixture of BaP plus NNK, but not by BaP. Dietary PEITC, or PEITC plus BITC, was more effective in these experiments than the compounds given by gavage. The results of this study demonstrate that proper doses of dietary PEITC and dietary as well as gavaged PEITC plus BITC are effective inhibitors of lung tumorigenesis induced in A/J mice by a mixture of BaP and NNK. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalCancer Letters
Volume150
Issue number1
DOIs
StatePublished - Mar 13 2000

Keywords

  • 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone
  • A/J mice
  • Benzo[a]pyrene
  • Benzyl isothiocyanate
  • Chemoprevention
  • Lung tumors
  • Phenethyl isothiocyanate

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