Carcinogenesis, Vol 18, 1715-1722, Copyright © 1997 by Oxford University Press
ME Staretz, LA Koenig and SS Hecht
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.
ARTICLES
Effects of long term dietary phenethyl isothiocyanate on the microsomal metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanol in F344 rats
American Health Foundation, Valhalla, NY 10595, USA.
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