Journal article
Polychlorinated biphenyls, classified as either phenobarbital- or 3-methylcholanthrene-type inducers of cytochrome P-450, are both hepatic tumor promoters in diethylnitrosamine-initiated rats
Cancer letters, Vol.32(3), pp.243-253
1986
DOI: 10.1016/0304-3835(86)90176-X
PMID: 3094931
Abstract
The cytochrome
P-450 isozymes, cytochrome
P-450 MC
1 and MC
2, purified from rats treated with 3-methylcholanthrene (MC), were found by immunohistochemical staining to be strongly induced in the livers of rats treated with 3,3′, 4,4′-tetrachlorobiphenyl (TCBP), while the cytochrome
P-450 isozymes, PB
1 and PB
2, purified from the livers of rats treated with phenobarbital (PB), were shown to be induced in the livers of rats treated with 2,2′, 4,4′, 5,5′-hexachlorobiphenyl (HCBP). The latter compound also strongly induced NADPH-cytochrome
P-450-reductase. Following induction, all 5 enzymes were located preferentially in the centrilobular and midzonal region of the liver acinus. The influence of these polychlorinated biphenyls (PCBs) on diethylnitrosamine (DEN)-initiated hepatocarcinogenesis was investigated by analyzing the evolution of adenosine triphosphatase-deficient focal lesions. Whereas DEN alone produced very few islets, the administration of either PCB congener (150 μmol/kg, i.p., once weekly over a period of 8 weeks) subsequent to DEN treatment (50 ppm in the drinking water, 10 days) strongly enhanced the number of islets as well as the relative volume of liver occupied by islet tissue. These effects were evident, both 1 and 9 weeks, after cessation of PCB treatment. Unexpectedly the less persistent PCB congener, TCBP, showed a much more potent enhancing effect after the 9 weeks recovery period than did (HCBP).
Details
- Title: Subtitle
- Polychlorinated biphenyls, classified as either phenobarbital- or 3-methylcholanthrene-type inducers of cytochrome P-450, are both hepatic tumor promoters in diethylnitrosamine-initiated rats
- Creators
- A Buchmann - Institute of Biochemistry, German Cancer Research Center, Im Neuenheimer Feld 280, D-6900 Heidelberg F.R.GW Kunz - Institute of Biochemistry, German Cancer Research Center, Im Neuenheimer Feld 280, D-6900 Heidelberg F.R.GC.R Wolf - Imperial Cancer Research Fund, Laboratory of Molecular Pharmacology and Drug Metabolism, University Department of Biochemistry, George Square, Edinburg EH8 9XD U.KF Oesch - Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasser 67, D-6500 Mainz F.R.GL.W Robertson - Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasser 67, D-6500 Mainz F.R.G
- Resource Type
- Journal article
- Publication Details
- Cancer letters, Vol.32(3), pp.243-253
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/0304-3835(86)90176-X
- PMID
- 3094931
- ISSN
- 0304-3835
- eISSN
- 1872-7980
- Language
- English
- Date published
- 1986
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984002447202771
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