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(148) Effects of dioxins on aryl hydrocarbon receptor-mediated responses in Baikal seals.
Iwata, Hisato*,1, Okajima, Yuka1, Watanabe, Mafumi1, Kim, Eun-Young1, Tanabe, Shinsuke1, Amano, Masao2, Miyazaki, Nobuyuki2, 1 Center for Marine Environmental Studies, Ehime University, Matsuyama, Ehime, Japan2 Marine Research Center, Ocean Research Institute, The University of Tokyo, Otsuchi, Iwate, Japan
ABSTRACT- In 1987-1988, outbreak of morbillivirus infection resulted in mass mortality of Baikal seals (Phoca sibirica). Immunosuppression elicited by chronic exposure to environmental contaminants in the seal species was suspected to be associated with the virus-induced mortality. However, the risk that the contaminants pose to the health of the seal population is uncertain, because of the lack of information on the direct link of chemical exposure with biochemical and adverse effects. Here we present the data on the levels of polychlorinated dibenzo-p-dioxins, dibenzofurans and coplanar polychlorinated biphenyls in Baikal seals. We also attempted to relate the dioxin levels with certain biochemical responses such as the activities of hepatic microsomal cytochrome P450 (CYP) and UDP-glucuronosyl transferase (UDPGT) in the seal population. The residue levels of dioxins were in the range of 180-800 pgTEQ/g wet wt in the seal blubber and of 9.9-570 pgTEQ/g wet wt in the liver. Baikal seals revealed an induction of EROD at lower TEQ levels (less than 200 pgTEQ/g wet wt), and a suppression at higher levels. There was a significant positive correlation between EROD and p-nitrophenol UDPGT activities. The NOEL value for EROD induction was estimated to be approximately 0.3 pgTEQ/g wet wt. A cross-reactive protein with polyclonal antibody against rat CYP1A1 was notably detected in the seal liver, while polyclonal antibody against rat CYP2B1 recognized a protein only at trace levels. Anti-rat CYP1A1 and CYP1B1 antisera inhibited EROD activity, but anti-rat CYP2B1 antiserum showed no inhibition. Furthermore, the cDNA encoding the aryl hydrocarbon receptor (AhR) from Baikal seal was identified. Our results indicate that the basic mechanism of AhR-mediated responses in Baikal seals is similar as that in experimental animals. Due to the high accumulation of dioxins and effects on the AhR-mediated responses, Baikal seal population may experience a serious threat from dioxins.
Key words: Dioxins, Baikal seal, Cytochrome P450, UDP-glucuronosyl transferase
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