Inducibility of AhR-regulated CYP genes by β-naphthoflavone in the liver, lung, kidney and heart of the pig

The presence and inducibility of CYP enzymes belonging to the family 1 (CYP1A1, 1A2 and 1B1) and AhR have been studied in liver, lung, kidney and heart of control and beta-naphthoflavone (beta NF)-treated pigs. Segments of so far undescribed genes for porcine CYP1A2, 1B1 and AhR were identified by RT-PCR and their sequences found to be highly homologous to those of the corresponding human genes. The mRNA level of CYP1A1 was induced by beta NF, although to a different extent, in liver, lung, kidney and heart. This transcriptional activation of CYP1 A1 was accompanied in microsomes of all these organs by an induction of 7-ethoxyresorufin deethylase activity (a marker of this isoform) and an increase in a protein band immunoreactive with anti-rat CYP1A1 An increase in CYP 1A2 transcription and in activity of microsomal 7-methoxyresorufin demethylase and acetanilide 4-hydroxylase (both markers of I A2) was observed in the liver and, to a very small extent, in the lung but not in kidney and heart. As to CYP1B1, its transcription was detected in liver, lung and heart only following the PNF treatment; however this mRNA expression did result i n any detectable microsomal 17 beta-estradiol 4-hydroxylase activity (a marker of this isoform). The CYPs induced by PNF were further investigated by using some other marker activities. It was found that porcine CYP1A1 and 1A2, unlike the human counterparts, could only deethylate 7-ethoxycomarin to a very small extent, if at all, whereas 7-ethoxy 4-trifluoroinethylcoumarin was a good substrate for pig CYP1A1. Overall, our results demonstrated a differential expression and regulation of the AhR-mediated CYP genes in liver, lung, kidney and heart of the pig naphthoflavone (C) 2007 Elsevier Ireland Ltd. All rights reserved.