Effect of phenethyl isothiocyanate on microsomal n-nitrosodimethylamine metabolism and other monooxygenase activities

H. Ishizaki, J. F. Brady, S. M. Ning, C. S. Yang

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Abstract

1. Phenethyl isothiocyanate (PEITC), a dietary compound derived from cruciferous vegetables, has previously been shown to decrease N-nitrosodimethylamine (NDMA)-induced methylation of hepatic DNA, apparently by inhibition of microsomal activation of the procarcinogen. 2. Using hepatic microsomes from acetone-treated rats, PEITC exhibited competitive inhibition of NDMA demethylase activity with an apparent Ki of 1 μm. In studies using a two-stage incubation protocol, the inhibition by PEITC was time- and metabolism-dependent. 3. Using control rat liver microsomes, PEITC selectively inhibited P450 IIE1-mediated NDMA-demethylase activity as compared to the demethylation of benzpheta-mine and ethylmorphine. 4. Pretreatment of rats with a single oral dose of PEITC (1 mmol/kg body wt) 24 h before killing caused a marked decrease in hepatic NDMA demethylase activity, but an 11-fold increase in 7-pentoxyresorufin O-dealkylase activity. These trends agreed with immunoblot analysis which indicated that PEITC was a suppressor of P450 IIE1 but an inducer of P450 IIB1. 5. The selective inhibition of P450 IIE1 activity and suppression of its level in microsomes indicates a role for PEITC as a chemopreventive agent against toxic or carcinogenic metabolites of this isozyme.

Original languageEnglish (US)
Pages (from-to)255-264
Number of pages10
JournalXenobiotica
Volume20
Issue number3
DOIs
StatePublished - 1990

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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