PW01 Wildlife Toxicology
Exhibit Hall
8:00 AM - Wednesday, 12 November 2003
(PW036) Quantitative analysis of the Ah receptor and CYP1A expression in Baikal seal liver contaminated by dioxins.
Kim, E-Y1, Ebisuda, K2, Iwata, H2, Sakamoto, T2, Tanabe, S2, Miyazaki, N3, 1 Ehime Prefectural Institute of Public Health and Environmental Science, Matsuyama, Ehime, Japan2 Center for Marine Environmental Studies, Ehime University, Matsuyama, Ehime, Japan3 Otsuchi Marine Research Center, Ocean Research Institute, The University of Tokyo, Iwate, Japan
ABSTRACT- The induction of P450 CYP1A/1B subfamilies involved in the metabolism of dioxins and its related planar halogenated aromatic hydrocarbons (PHAHs) have been used as a sensitive biomarker to measure the effects of exposure to these chemicals in various organisms. The aryl hydrocarbon receptor (AhR), a transcriptional factor that responds to planar aromatic ligands, plays a central role in CYP1A-mediated reactions. The quantitative relationships among PHAH residue levels, AhR expression and CYP1A induction, which are inconsistent and depend on cell- and tissue-types, are not yet clear in wildlife including aquatic mammals. In this study, to understand the quantitative relationship of AhR-CYP1A/1B signaling pathway in aquatic mammals, we determined the AhR mRNA levels in the liver of Baikal seals which accumulate the high levels of PHAHs, using real time RT-PCR method. We further evaluated the relationship between AhR mRNA level and the hepatic PHAH residue levels and CYP1A induction. The expression level of AHR mRNA was not affected by increased exposure to total TEQ. On the other hand, the AHR mRNA level showed a positive correlation with the CYP1A protein level (p=0.039), although no correlation with CYP1B protein levels was found. These results suggest that the residue level of PHAHs is not only a crucial factor to regulate the transcriptional level of AHR, but the AHR activated by PHAHs is involved in the expression of CYP1A in Baikal seal. Considering the fact that total TEQ revealed a significant positive correlation with CYP1A level (p = 0.0001), rather than AHR level (p=0.24), it can be concluded that the major PHAH congeners may bind to CYP1A, and this may subsequently lead to their hepatic sequestration.
Key words: CYP1A1, AhR