TY - JOUR T1 - Effect of Breed upon Cytochromes P450 and Phase II Enzyme Expression in Cattle Liver JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 885 LP - 893 DO - 10.1124/dmd.107.019042 VL - 36 IS - 5 AU - Mery Giantin AU - Monica Carletti AU - Francesca Capolongo AU - Sara Pegolo AU - Rosa Maria Lopparelli AU - Federica Gusson AU - Carlo Nebbia AU - Michela Cantiello AU - Pascal Martin AU - Thierry Pineau AU - Mauro Dacasto Y1 - 2008/05/01 UR - http://dmd.aspetjournals.org/content/36/5/885.abstract N2 - Cattle represent an important source of animal-derived food-products; nonetheless, our knowledge about the expression of drug-metabolizing enzymes (DMEs) in present and other food-producing animals still remains superficial, despite the obvious toxicological consequences. Breed represents an internal factor that modulates DME expression and catalytic activity. In the present work, the effect of breed upon relevant phase I and phase II DMEs was investigated at the pretranscriptional and post-translational levels in male Charolais (CH), Piedmontese (PM) and Blonde d'Aquitaine (BA) cattle. Because specific substrates for cattle have not yet been identified, the breed effect upon specific cytochrome P450 (P450), UDP-glucuronosyltransferase (UGT), or glutathione S-transferase (GST) DMEs, in terms of catalytic activity, was determined by using human marker substrates. Among P450s, benzphetamine N-demethylase, 16β-, 6β-, and 2β-testosterone hydroxylase, aniline and p-nitrophenol hydroxylase, and α-naphthol and p-nitrophenol UGT activities were significantly higher in CH; in contrast, lower levels of CYP1A1-, CYP1A2-, CYP2B6-, CYP2C9-, CYP2C18-, CYP3A4-, and UGT1A1-like mRNAs were noticed, with CH < PM ≤ BA as a trend. CYP2B and CYP3A mRNA results were confirmed with immunoblotting, too. As regards conjugative DMEs, UGT1A6-like mRNA levels were consistent with respective catalytic activities. Both 1-chloro-2,4-dinitrobenzene and 3,4-dichloronitrobenzene GST activities were higher in BA, and these results agreed with GSTA1-, GSTM1-, and GSTP1-like mRNA amounts. Correlation analysis between catalytic activities and mRNAs showed either significant or uneven results, depending on the substrate. These findings confirm previous data obtained in laboratory species; however, further studies are required to ascribe this behavior to pretranscriptional or post-translational phenomena. The American Society for Pharmacology and Experimental Therapeutics ER -