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

Phenethyl isothiocyanate (PEITC) is an effective inhibitor of lung tumorige nesis induced,in rats and mice by the tobacco-specific carcinogen 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) while benzyl isothiocyanate (BI TC) inhibits lung tumorigenesis induced in mice by another tobacco smoke ca rcinogen, benzo[a]pyrene (BaP). However, little is known about the inhibito ry 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 car ried out a series of experiments pertinent to these questions. In Experimen t 1, treatment of A/J mice with PEITC (6 mu mol), BITC (6 mu mol), or a com bination of the two (6 mu mol each) by gavage, 2 h prior to each of eight w eekly gavage treatments with a mixture of BaP and NNK (3 mu mol of each), h ad no effect on lung tumor multiplicity. In Experiment 2, we evaluated the inhibitory potential of four different mixtures of PEITC and BITC, administ ered by gavage 2 h prior to each of eight weekly doses of BaP and NNK, as g iven in Experiment 1. Mixtures of PEITC and BITC (12 mu mol of each, or 12 mu mol PEITC and 9 mu mol BITC) significantly reduced lung tumorigenesis in duced by a mixture of BaP and NNK. In Experiment 3, we investigated the eff ects of dietary PEITC (3 mu mol/g diet), BITC (1 mu mol/g diet), or a mixtu re of PEITC (3 mu mol/g diet) and BITC (1 mu mol/g diet). These compounds w ere 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 signif icantly inhibited lung tumor multiplicity; inhibition was due mainly to PEI TC. In Experiment 4, we tested dietary PEITC (3, 1, or 0.3 mu mol/g diet) a s an inhibitor of lung tumorigenesis induced by BaP, NNK, or BaP plus NNK u sing a protocol identical to that in Experiment 3. PEITC was an effective i nhibitor of lung tumor multiplicity induced by NNK and a mixture of BaP plu s NNK, but not by BaP. Dietary PEITC, or PEITC plus BITC, was more effectiv e in these experiments than the compounds given by gavage. The results of t his study demonstrate that proper doses of dietary PEITC anti dietary as we ll as gavaged PEITC plus BITC are effective inhibitors of lung tumorigenesi s induced in A/J mice by a mixture of BaP and NNK. (C) 2000 Elsevier Scienc e Ireland Ltd. All rights reserved.