The influence of diet composition on phase I and II biotransformation enzyme induction

Abstract

The expression of phase I and II biotransformation enzymes was examined with respect to experimental diet composition and with the addition of the bi-functional inducer flavone. Enzymatic activity and mRNA levels of cytochrome P450 monooxygenase (CYP) isoforms (CYP1A1, CYP1A2, CYP2B1/2) and glutathione-S-transferase (GST) isoforms (GSTA, GSTM, and GSTP) were used as indices for the changes in expression. An amino acid based (AA) diet and a semi-purified egg white (EW) diet were designed to include similar levels of nutrients and were compared to a standard laboratory chow (SC) diet. Rats (Sprague-Dawley) and mice (C57BL/6) were used as animal models. Animals were fed one of the three diets for 7 days prior to incorporation of flavone (2%, wt/wt). Diets with or without flavone were next fed for an additional 3 days. Enzymatic activities of the CYPs in mice and GSTs in both mice and rats were determined. In mice, the relative mRNA levels for each of the CYP and GST isoforms were also measured. The increase in phase I and II enzyme expression observed in response to flavone was most dynamic when the AA-based diet was used (often >20-fold for given isoform enzymatic activities and >200-fold for specific mRNAs), followed by the EW diet (10 to 20-fold and 100 to 200-fold, respectively). The SC diet resulted in a higher level of background expression of CYP and GST isoforms and as a consequence the observed fold increases in CYP and GST isoforms (enzymatic and mRNA levels) were substantially less (1 to 10-fold and 1 to 150-fold. respectively), when the SC diet fed group with or without flavone was compared.