Octachlorostyrene Induces Cytochrome P450, UDP-glucuronosyltransferase, and Sulfotransferase via the Aryl Hydrocarbon Receptor and Constitutive Androstane Receptor
Open Access
- 12 June 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Toxicological Sciences
- Vol. 111 (1), 19-26
- https://doi.org/10.1093/toxsci/kfp130
Abstract
Octachlorostyrene (OCS) is a byproduct produced in the process of synthesis of chlorinated compounds. There are some reports concerning environmental contamination by OCS, but few on the toxicological effects on human. Drug-metabolizing enzymes may play an important role in toxicity through metabolic activation or deactivation of OCS. In this study, we investigated whether OCS influences these enzymes using wild-type and aryl hydrocarbon receptor (Ahr)-null mice; AhR regulates cytochrome P450 (CYP) 1A, UDP-glucuronosyltransferase (UGT), or sulfotransferase (SULT). Both mouse lines were treated with OCS (0, 32, and 64 μmol/kg) for 4 days by gavage. As a reference, the mice were treated with 20 mg/kg 3-methylcholanthrene (3MC) for 4 days. OCS treatment increased the expression of CYP 1A1 and CYP1A2 mRNA and ethoxyresorfin O-deethylase activity only in the wild-type mice, similar to that of the AhR activator 3MC. OCS treatment increased expression of UGT1A6 and SULT 1A1 mRNA and their associated enzyme activities only in Ahr-null mice, whereas 3MC still influenced these enzymes only in wild-type mice. OCS induced constitutive androstane receptor (CAR) only in Ahr-null mice, and the target gene CYP2B10 mRNA was induced more strongly in Ahr-null mice than in wild-type mice. 3MC slightly induced CYP2B10 mRNA only in the wild-type mice. These results suggest that CAR is involved in regulation of the UGT and SULT genes by OCS. Thus, OCS may regulate CYP1A via AhR, whereas it controls UGT1A6 and SULT1A via CAR.Keywords
This publication has 25 references indexed in Scilit:
- Pyrene-induced CYP1A2 and SULT1A1 may be regulated by CAR and not by AhRToxicology, 2007
- The distribution of octachlorostyrene (OCS) in environmental samples from EuropeJournal of Environmental Monitoring, 2003
- Chlorostyrenes in fish and sediment samples from the river ElbeChemosphere, 1998
- Xenobiotic Responsive Element-mediated Transcriptional Activation in the UDP-glucuronosyltransferase Family 1 Gene ComplexPublished by Elsevier BV ,1996
- Immune System Impairment and Hepatic Fibrosis in Mice Lacking the Dioxin-Binding Ah ReceptorScience, 1995
- Organochlorine pesticides, octachlorostyrene, and mercury in the blood of Elb River residents, GermanyArchives of Environmental Contamination and Toxicology, 1992
- Long-term toxicity of octachlorostyrene in the ratFundamental and Applied Toxicology, 1986
- Organochlorines and Mercury in Blood of a Fish-Eating Population at the River Elbe in Schleswig-Holstein, FRGArchives of Toxicology, 1985
- Octachlorostyrene: A 90-day toxicity study in the ratFundamental and Applied Toxicology, 1984
- Human blood samples as indicators of occupational exposure to persistent chlorinated hydrocarbonsScience of The Total Environment, 1977