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

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.

Dioxin‐like and perfluorinated compounds in pigs in an Indian open waste dumping site: Toxicokinetics and effects on hepatic cytochrome P450 and blood plasma hormones

“…The concentration ratios of certain congeners (congener x/PCB169) had negative correlations with CYP1A-like protein content, possibly as a result of preferential metabolism, as reported for some other species [14,15,40]. In pigs, the concentration ratio of PCB114 showed a significant negative correlation with CYP1A-like protein levels (r ¼ À0.44, p < 0.05).…”

Tissue‐based risk assessment of great blue heron (Ardea herodias) exposed to PCDD/DF in the Tittabawassee River floodplain, Michigan, USA

“…Field studies have reported negligible bioaccumulation of TCDF from prey items in Forster's terns and herring gulls [7,50]. This may be attributable to preferential metabolism of 2,3,7,8-TCDF, which a number of studies have reported in various avian species exposed to mixtures of AhR-active compounds [51][52][53]. Data on avian toxicokinetics from controlled laboratory studies are limited, but mammalian studies have shown the rate of metabolism of 2,3,7,8-TCDF to be elevated with increased concentrations of dioxin-like compounds and the subsequent induction of cytochrome P450 1A1 or 1A2, whereas 2,3,4,7,8-PeCDF is preferentially sequestered in the liver [54,55].…”

Catalytic function of avian cytochrome P450 1A4 and 1A5 (CYP1A4 and CYP1A5) enzymes heterologously expressed using in vitro yeast system

“…Furthermore, we have clarified that cormorants collected from Lake Biwa in Japan accumulate high levels of DRCs in the liver and induce CYP1A4 and 1A5 at transcriptional and translational levels (Kubota et al, 2004(Kubota et al, , 2005(Kubota et al, , 2006. While extensive data are available on mammalian CYP1A1 and 1A2, enzymatic properties of CYP1A4 and 1A5 isozymes in avian species have been poorly understood until now.…”

“…Expression of recombinant CYP1A proteins in yeast microsomes was confirmed by the reduced CO-difference spectrum and detected by western blotting. Kinetics and specificity of the CYP1A enzymes toward O-dealkylation of methoxy-, ethoxy-, pentoxy-and benzyloxyresorufin (MROD, EROD, PROD and BROD, respectively) were investigated as described by Kubota et al (2005) with some modifications.…”

“…Expression of recombinant CYP1A proteins in yeast microsomes was confirmed by the reduced CO-difference spectrum and detected by western blotting. Kinetics and specificity of the CYP1A enzymes toward O-dealkylation of methoxy-, ethoxy-, pentoxy-and benzyloxyresorufin (MROD, EROD, PROD and BROD, respectively) were investigated as described by Kubota et al (2005) with some modifications.Yeast microsomes containing each common cormorant CYP1A enzyme showed quantifiable Soret maximum at 446 nm. The concentrations of CYP1A4 and 1A5 proteins were estimated to be 351 and 275 pmol/mg protein, respectively.…”