Phenethyl isothiocyanate (
PEITC), a cruciferous vegetable component, inhibits lung
tumor induction by the tobacco specific
nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). To gain insight into the mechanism of
PEITC lung
tumor inhibition, we examined, in male F344 rats, the effects of dietary
PEITC (3 micromol/g NIH-07 diet) in combination with NNK treatment (1.76 mg/kg, s.c., three times a week) for 4, 12 and 20 weeks on liver and lung microsomal metabolism of NNK and
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a major metabolite of NNK and also a lung
carcinogen. This was compared with rats fed NIH-07 diet, without
PEITC, and treated with NNK alone or saline. The protocol was identical to that employed for inhibition of lung
tumorigenesis by
PEITC. We observed decreased rates of alpha-hydroxylation of NNK and NNAL in lung microsomes of 4-, 12- and 20-week
PEITC + NNK treated rats compared with those treated with NNK or saline. NNK treatment alone also decreased lung alpha-methylene hydroxylation of NNK. Long-term NNK +
PEITC administration did not significantly affect liver oxidative metabolism of NNK or NNAL, and did not affect the rate of glucuronidation of NNAL in liver microsomes when compared with rats treated with NNK or saline. Thus,
PEITC selectively inhibited lung metabolic activation of NNK and NNAL. These results support the hypothesis that
PEITC inhibits NNK-induced lung
tumors by inhibiting metabolic activation of NNK in the lung. This study also demonstrated that
PEITC inhibits lung alpha-hydroxylation of NNAL; this may play a role in
PEITC inhibition of lung
tumorigenesis by NNK.