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 micromol), BITC (6 micromol), or a combination of the two (6 micromol each) by gavage, 2 h prior to each of eight weekly gavage treatments with a mixture of BaP and NNK (3 micromol 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 micromol of each, or 12 micromol
PEITC and 9 micromol BITC) significantly reduced lung
tumorigenesis induced by a mixture of BaP and NNK. In Experiment 3, we investigated the effects of dietary
PEITC (3 micromol/g diet), BITC (1 micromol/g diet), or a mixture of
PEITC (3 micromol/g diet) and BITC (1 micromol/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 micromol/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.