Low Induction Potencies of Cytochrome P450 2B and 3A by Persistent Organic Pollutants in Baikal Seal (Pusa sibirica)

To assess the potential effects of persistent organic pollutants (POPs) on the expression of cytochrome P450 (CYP) 2B and 3A isozymes in Baikal seal, the 5′-flanking regions of these CYP genes were isolated, and transactivation analysis was performed by in vitro reporter gene assay system. The 3.2 kbp of CYP2B and 2.2 kbp of CYP3A gene promoter/enhancer regions were cloned and sequenced from Baikal seal (Pusa sibirica). The phenobarbital responsive enhancer module-like sequence and the everted repeat 6 motif were identified in the seal CYP2B and 3A promoter/enhancer regions, respectively. The reporter gene assay demonstrated that treatment with a classical agonist for human CAR (CITCO) or PXR (SR12813) induced both CYP2B and 3A transcriptional activities via seal CAR and PXR. These results indicate that the CAR-CYP2B and PXR-CYP3A signaling pathways and their cross-talk mechanisms are conserved in Baikal seal as well as other mammalian species. Treatment with p,p′-DDT or p,p′-DDE led to only a slight increase in CYP2B transcriptional activity in seal PXR-dependent manner, and no increase in seal CAR-dependent manner. PCBs treatment showed no CYP2B induction via seal CAR or PXR. As for CYP3A gene, no seal CAR/PXR-dependent transcriptional activity was detected in any POPs. These results suggest low induction potencies of CYP2B and 3A by POPs via Baikal seal CAR and PXR.