Journal article
Effects of polychlorinated biphenyls in rat liver: Correlation between primary subcellular effects and promoting activity
Toxicology and applied pharmacology, Vol.111(3), pp.454-468
1991
DOI: 10.1016/0041-008X(91)90250-I
PMID: 1684070
Abstract
In the present study the promoting activity of various PCB and PBB isomers and congeners in rat liver has been studied and compared with a variety of primary xenobiotic-mediated enzymatic changes in this target organ. Female Wistar rats were given diethylnitrosamine (DEN; 10 mg/kg body wt for 10 days) and were subsequently treated once weekly with polychlorinated biphenyls (150 or 15 μmol/kg body wt) for a total of 8 weeks. Additional groups of rats were administered 3,3′,4,4′-tetrabromobiphenyl or 3-methylcholanthrene (8 weekly injections of 15 or 150 μmol/kg body wt, respectively) or were given phenobarbital (0.05% in the diet) until the end of the experiment. Reference groups were treated with the various test compounds without prior initiation. One week and 9 weeks after cessation of promoter treatment rats were killed and the volumetric fraction of enzyme-altered foci characterized by changes in adenosine triphosphatase and γ-glutamyl transpeptidase activity was determined as a means to quantitatively assess the extent of preneoplastic response in this organ. Out of the series of polyhalogenated biphenyls tested, promoting effects were seen with the following compounds: 2,2′,4,5′-tetrachlorobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl, 2,3,4,4′,5-pentachlorobiphenyl, and 3,3′,4,4′-tetrabromobiphenyl, whereas no significant effects were obtained with 4-monochlorobiphenyl. In rats not treated with DEN, the two strongly promoting agents 2,3,4,4′,5-pentachloribiphenyl and 3,3′,4,4′-tetrachlorobiphenyl also significantly increased the volume fraction of enzyme-altered foci over the respective controls when analyzed at the second time point of investigation. In parallel experiments, induction of liver growth and of microsomal cytochrome P450 content in liver was found to correlate well with the promoting activity of the various xenobiotics, suggesting that these parameters may be used to predict the promoting activity of polyhalogenated biphenyls in a short term assay.
Details
- Title: Subtitle
- Effects of polychlorinated biphenyls in rat liver: Correlation between primary subcellular effects and promoting activity
- Creators
- Albrecht Buchmann - German Cancer Research Center, Institute of Experimental Pathology, Im Neuenheimer Feld 280, 6900 Heidelberg, Federal Republic of GermanySusanne Ziegler - German Cancer Research Center, Institute of Experimental Pathology, Im Neuenheimer Feld 280, 6900 Heidelberg, Federal Republic of GermanyArmin Wolf - German Cancer Research Center, Institute of Experimental Pathology, Im Neuenheimer Feld 280, 6900 Heidelberg, Federal Republic of GermanyLarry W Robertson - University of Kentucky, Graduate Center for Toxicology, Lexington, Kentucky USAStephen K Durham - Squibb Institute for Medical Research, Princeton, New Jersey USAMichael Schwarz - German Cancer Research Center, Institute of Experimental Pathology, Im Neuenheimer Feld 280, 6900 Heidelberg, Federal Republic of Germany
- Resource Type
- Journal article
- Publication Details
- Toxicology and applied pharmacology, Vol.111(3), pp.454-468
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0041-008X(91)90250-I
- PMID
- 1684070
- ISSN
- 0041-008X
- eISSN
- 1096-0333
- Language
- English
- Date published
- 1991
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984002302602771
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