Hepatic CYP1A Induction by Dioxin-like Compounds, and Congener-Specific Metabolism and Sequestration in Wild Common Cormorants from Lake Biwa, Japan

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Abstract

The present study examines the effects of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) on hepatic cytochromes P450 (CYP) in the wild population of common cormorants from Lake Biwa, Japan, and discusses functional roles of CYP1A in terms of correlation analysis between tissue concentrations of individual congeners and expression levels of CYP1A. Levels of alkoxyresorufin (methoxy-, ethoxy-, pentoxy-, and benzyloxyresorufin) O-dealkylase activities and a protein cross-reacted with anti-rat CYP1A1 polyclonal antibodies showed significant positive correlations with total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) or TEQs for most individual congeners in the liver of cormorants, suggesting induction of CYP1A-like protein by these chemicals. In contrast, TEQs for lower chlorinated congeners, 2,3,7,8-T4CDF and PCB77, showed relatively low correlations with the expression level of CYP1A-like protein. Concentrations of 2,3,7,8-T4CDF and PCB77 normalized to a relatively recalcitrant congener, PCB169, were negatively correlated with the CYP1A-like protein level. These results indicate preferential metabolism of those congeners by CYP1A-like protein that was induced by TEQs. Concentration ratios of liverto pectoral muscle for certain congeners significantly increased with an elevation of the CYP1A-like protein level. Comparing the results in the present study with those of previous studies using rodents treated with certain dioxin-like congeners, these congeners in the liver may be sequestered by CYP1A. Levels of cross-reactive proteins with anti-rat CYP2B1, CYP2C6, and CYP3A2 polyclonal antibodies correlated with neither TEQs nor liver/muscle concentration ratios of congeners. We conclude that the potential for CYP1A induction, and metabolism and sequestration of dioxin-like compounds by CYP1A, may be a critical factor for assessing the ecological risk in wild avian species.

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