EFFECTS OF ISOTHIOCYANATES ON THE METABOLISM OF 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE (NNK) AND BENZO[A]-PYRENE BY HAMSTER AND RAT-LIVER MICROSOMES

Benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC) stro ngly inhibited the N-pyridine oxidation and alpha-carbon hydroxylation pathways of the in vitro metabolism of the tobacco-specific nitrosami ne 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by Syrian gold en hamster liver microsomes from saline-injected (noninduced) animals. PEITC was more potent than BITC. NNK-reduction was enhanced by both i sothiocyanates. Both N-oxidation and alpha-hydroxylation activities we re several-fold greater in hamster liver microsomes compared with F344 rat liver microsomes. Consequently, the inhibitory effect of BITC and PEITC on rat liver microsomes (noninduced) was not as pronounced. NNK -reduction in rat liver microsomes was not significantly different fro m hamster and was not enhanced by BITC and PEITC. Neither BITC nor PEI TC had a strong inhibitory effect on the in vitro metabolism of benzo[ a]pyrene (BaP) by either hamster or F344 rat liver microsomes from bet a-naphthoflavone treated animals. The extent of BaP metabolism was sim ilar for the two microsome groups. Since the metabolism of NNK and BaP depends upon cytochrome P450-mediated reactions that may utilize diff erent isozymes of cytochrome P450, our data suggest that BITC and PEIT C may inhibit the activity of some isozymes and not others. Our result s also indicate that the inhibition of the metabolism of NNK by isothi ocyanates as previously described for the mouse and rat can now be ext ended to include the hamster as well.