2004 Volume 7 Issue 2 Pages 55-59
Baikal seal (Pusa sibirica) accumulates high levels of environmental contaminants such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and coplanar polychlorinated biphenyls (Co-PCBs). In mammalian species, the toxic effects of these chemicals are posed by the modulation of transactivation of multiple target genes including cytochrome P450 (CYP) 1A1 and 1A2 mediated by the aryl hydrocarbon receptor. In order to clarify whether CYP1A1 and CYP1A2 are induced by these dioxin-like congeners in wild Baikal seals, this study attempted to identify these CYP cDNAs and to analyze relationships between the hepatic concentrations of PCDDs/DFs/Co-PCBs and CYP1A1/1A2 mRNA expression levels in the seal population. The full-length CYP1A1 and 1A2 cDNAs were isolated from the liver of Baikal seal. CYP1A1 cDNA encoded 517 amino acid residues with a predicted molecular mass of 58.3 kDa, and CYP1A2 cDNA encoded 512 amino acid residues with a predicted molecular mass of 57.8 kDa. Both CYP1A1 and 1A2 mRNA levels showed significant positive correlations with total TEQs and the majority of individual congener TEQs. Lower correlations were found for 2,3,7,8-T4CDD/DF, O8CDD, PCB77, PCB169, and mono-ortho Co-PCB congeners. This indicated preferential metabolism of 2,3,7,8-T4CDD/DF and PCB77 by induced CYP1A1/1A2, and lower CYP induction potentials as for other congeners. The mRNA levels of CYP1A1/1A2 revealed significant positive correlations with CYP1A-like protein levels, which were immunochemically detected by anti-rat CYP1A1 polyclonal antibody, suggesting that the CYP1A-like protein levels reflect both CYP1A1 and CYP1A2 mRNA levels. These results revealed that both CYP1A1 and 1A2 are induced by PCDDs/DFs/Co-PCBs at transcriptional and translational levels in the liver of Baikal seals.
