Transactivation Potencies of Baikal Seal Constitutive Active/Androstane Receptor by Persistent Organic Pollutants and Brominated Flame Retardants

• Published in: Environmental science & technology Vol. 43; no. 16; pp. 6391 - 6397
• Main Authors: Sakai, Hiroki, Kim, Eun-Young, Petrov, Evgeny A, Tanabe, Shinsuke, Iwata, Hisato
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 15-08-2009
• Subjects: Animals; Binding sites; Caniformia - genetics; Chemical compounds; Ecotoxicology and Human Environmental Health; Environmental Pollutants - toxicity; Flame retardants; Flame Retardants - toxicity; Genes; Genes, Reporter; Hydrocarbons, Brominated - toxicity; Ligands; Marine; Marine mammals; Mice; Organic chemicals; Organic Chemicals - toxicity; PCB; Pollutants; Polychlorinated biphenyls; Proteins; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Species Specificity; Transcriptional Activation - drug effects
• ISSN: 0013-936X; 1520-5851
• DOI: 10.1021/es901120r

To characterize ligand-dependent transcriptional activation of constitutive active/androstane receptor (CAR) in aquatic mammals, transactivation potentials of the Baikal seal (Pusa sibirica) CAR (bsCAR) by environmental pollutants, including persistent organic pollutants (POPs) and brominated flame retardants (BFRs), were investigated using an in vitro reporter gene assay, and compared with those of the mouse CAR (mCAR). Measurement of luciferase reporter gene activities demonstrated that the seal CAR was activated by POPs, including a technical mixture of PCBs (Kanechlor-500), certain individual PCB congeners, DDT compounds, and trans-nonachlor. No or slight bsCAR-dependent activity was detected in experiments with PBDE congeners and HBCDs. The interspecies comparison of lowest observed effect concentration (LOEC) for CAR transactivation by each compound revealed that bsCAR responds more sensitively to PCBs than mCAR. In addition, bsCAR was weakly deactivated by PBDE99, whereas mCAR transcriptional activity decreased weakly by PBDE100, PBDE154, and PBDE187. Comparison of reporter gene activities by the congeners with the same IUPAC numbers among PCBs and PBDEs revealed that both bsCAR and mCAR were not activated by PBDE99 and PBDE153, but were activated by PCB99 and PCB153. The small ligand-binding pocket in CAR may contribute to difference in response between PCBs and PBDEs. Given that ethical rationale prevents dosing studies with such organohalogens in aquatic mammals, our in vitro assay system constructed with CAR cDNA from a species of interest provides a useful and realistic alternative approach in ecotoxicology.