Significant interspecies differences in induction profiles of hepatic CYP enzymes by TCDD in bank and field voles

Abstract

The gene expression and induction of cytochrome P450 (CYP)-enzymes following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) peroral administration was studied in the livers of two wild vole species--the bank vole (Myodes glareolus) and the field vole (Microtus agrestis). The dioxin-sensitive C57BL/6 mouse was used as a reference. Doses of 0.05, 0.5, 5.0, and 50 µg/kg were applied to ascertain a dose-response relationship, and the dose of 50 µg/kg was applied to the study time course for up to 96 h. The cytochrome P450 1A1 (CYP1A1) mRNA expression showed an expected dose-dependent increase equally in both vole species. Bank voles expressed notably higher CYP2A mRNA levels as compared with field voles. Both species exhibited dose-dependent increases in putative CYP1A-, CYP2B-, and CYP2A-associated activities as measured by fluorometric assays for ethoxyresorufin-O-deethylase (EROD), penthoxyresorufin-O-depenthylase (PROD), and 7-ethoxycoumarin-O-deethylase (ECOD), respectively. Putative CYP2A-associated coumarin-7-hydroxylase (COH) activity showed a slight increase at the two highest doses of TCDD in field voles but not in bank voles, and their basal COH activity was only one-fourth or less of that in field voles. Overall, however, bank voles tended to exhibit higher CYP-associated enzyme activities measured at the two largest doses of TCDD than field voles. A western blot analysis of aryl hydrocarbon receptor (AhR) revealed that the two vole species had differential band patterns, suggesting dissimilar structures for their AhRs.

Effects of pentachlorophenol on the quail ( Coturnix japonica ) liver detoxification pathway

“…CYP2A-, CYP2B-, and CYP3A-associated activities, as measured by fluorometric assays for ECOD, PROD, and END, respectively, have been reported in previous research (Murtomaa-Hautala et al, 2012;Liang et al, 2013). Our results showed that PCP exposure significantly induced ECOD expression at dosages of 0.5 and 5 mg/kg/d, whereas PROD and END activities were markedly inhibited in the 0.5 mg/kg/d PCP-treated group.…”

Accumulation properties of polychlorinated biphenyl congeners in Yusho patients and prediction of their cytochrome P450-dependent metabolism by in silico analysis

“…We have shown that human CYP1A1, CYP2A6, and CYP2B6 have the potential to metabolize PCB congeners. In addition, CYP1A1 and CYP2A6 are induced by an aryl hydrocarbon receptor- mediated pathway (Arpiainen et al 2005; Murtomaa-Hautala et al 2012; Nebert et al 2000; Okino and Whitlock 2000). Because the concentration of PCDFs in the blood of Yusho patients is still higher than that of controls, these isozymes may be involved in the characteristic accumulation patterns of PCB congeners in the blood of Yusho patients.…”