Journal article
Biological and Tumor-Promoting Effects of Dioxin-like and Non-Dioxin-like Polychlorinated Biphenyls in Mouse Liver After Single or Combined Treatment
Toxicological sciences, Vol.133(1), pp.29-41
05/2013
DOI: 10.1093/toxsci/kft034
PMCID: PMC3627557
PMID: 23457121
Abstract
To assess the impact of a mixture containing dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs), male mice were initiated with N-nitroso-diethylamine and subsequently treated with PCB126, an Ah-Receptor agonist, and PCB153, acting via activation of the constitutive androstane receptor. The two congeners were given at two dose levels: the low dose was adjusted to induce ~150-fold increases in cytochrome P450 (Cyp)1a1 (PCB126) and Cyp2b10 mRNAs (PCB153), and the high dose was chosen as twice the low dose. To keep the liver PCB levels constant, mice were given initial loading doses followed by weekly maintenance doses calculated on the basis of the PCBs’ half-lives. Mice were treated with the individual congeners (low and high dose) or with a mixture consisting of the low doses of the 2 PCBs. The following results were obtained: (1) the 2 PCBs produced dose-dependent increases in Cyp1a1 and Cyp2b10 mRNA, protein, and activity when given individually; (2) combined treatment caused more than additive effects on Cyp1a1 mRNA expression, protein level, and ethoxyresurofin activity; (3) changes in the levels of several proteins were detected by proteome analysis in livers of PCB-treated mice; (4) besides these biological responses, the individual PCBs caused no significant increase in the number of glucose-6-phospatase (G6Pase)–deficient neoplastic lesions in liver, whereas a moderate significant effect occurred in the combination group. These results suggest weak but significant response-additive effects of the 2 PCBs when given in combination. They also suggest that the Cyp biomarkers tend to overestimate the carcinogenic response produced by the PCBs in mouse liver.
Details
- Title: Subtitle
- Biological and Tumor-Promoting Effects of Dioxin-like and Non-Dioxin-like Polychlorinated Biphenyls in Mouse Liver After Single or Combined Treatment
- Creators
- Benjamin Rignall - Department of Toxicology, University of TübingenKonstanze Grote - Department of Experimental Medicine, Charité Universitätsmedizin BerlinAlina Gavrilov - Department of Toxicology, University of TübingenMarc Weimer - German Cancer Research Center, Central Unit of BiostatisticsAnnette Kopp-Schneider - German Cancer Research Center, Central Unit of BiostatisticsEberhard Krause - Leibniz Institute for Molecular Pharmacology (FMP)Klaus E Appel - Federal Institute for Risk Assessment, Unit of Food ToxicologyAlbrecht Buchmann - Department of Toxicology, University of TübingenLarry W Robertson - Department of Occupational and Environmental Health, College of Public Health, University of IowaHans-Joachim Lehmler - Department of Occupational and Environmental Health, College of Public Health, University of IowaIzabela Kania-Korwel - Department of Occupational and Environmental Health, College of Public Health, University of IowaIbrahim Chahoud - Institute of Clinical Pharmacology and Toxicology, Charité Universitätsmedizin BerlinMichael Schwarz - Department of Toxicology, University of Tübingen
- Resource Type
- Journal article
- Publication Details
- Toxicological sciences, Vol.133(1), pp.29-41
- DOI
- 10.1093/toxsci/kft034
- PMID
- 23457121
- PMCID
- PMC3627557
- NLM abbreviation
- Toxicol Sci
- ISSN
- 1096-6080
- eISSN
- 1096-0929
- Publisher
- Oxford University Press; US
- Language
- English
- Date published
- 05/2013
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
- Record Identifier
- 9984001081502771
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