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Toxicology. 2007 Oct 30;240(1-2):25-37. Epub 2007 Jul 24.

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

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  • 1Istituto di Fisiologia Clinica, CNR, via Moruzzi 1, 56100 Pisa, Italy.

Abstract

The presence and inducibility of CYP enzymes belonging to the family 1 (CYP 1A1, 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 CYP 1A2, 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 CYP 1A1 was induced by beta NF, although to a different extent, in liver, lung, kidney and heart. This transcriptional activation of CYP 1A1 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 CYP 1A1. An increase in CYP 1A2 transcription and in activity of microsomal 7-methoxyresorufin demethylase and acetanilide 4-hydroxylase (both markers of 1A2) was observed in the liver and, to a very small extent, in the lung but not in kidney and heart. As to CYP 1B1, its transcription was detected in liver, lung and heart only following the beta NF treatment; however this mRNA expression did result in any detectable microsomal 17beta-estradiol 4-hydroxylase activity (a marker of this isoform). The CYPs induced by beta NF were further investigated by using some other marker activities. It was found that porcine CYP 1A1 and 1A2, unlike the human counterparts, could only deethylate 7-ethoxycomarin to a very small extent, if at all, whereas 7-ethoxy 4-trifluoromethylcoumarin was a good substrate for pig CYP 1A1. 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.

PMID:
17804143
[PubMed - indexed for MEDLINE]
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