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Lack of covalent binding to rat liver DNA of the hypolipidemic drugs clofibrate and fenofibrate

Please always quote using this URN: urn:nbn:de:bvb:20-opus-61087
  • \(^{14}\)C-Labelled clofibric acid and fenofibric acid were administered p.o. to 200 g male and female rats. After 10 h, liver nuclear DNA and protein were isolated and the radioactivity was determined. Binding to protein was clearly measurable whereas no binding to DNA could be detected from any drug. A comparison of the Iimit of detection of such DNA binding with well-known chemical carcinogens revealed that the known hepatocarcinogenicity of clofibrate cannot be based upon an initiating, DNA damaging, mode of action but must be due to other,\(^{14}\)C-Labelled clofibric acid and fenofibric acid were administered p.o. to 200 g male and female rats. After 10 h, liver nuclear DNA and protein were isolated and the radioactivity was determined. Binding to protein was clearly measurable whereas no binding to DNA could be detected from any drug. A comparison of the Iimit of detection of such DNA binding with well-known chemical carcinogens revealed that the known hepatocarcinogenicity of clofibrate cannot be based upon an initiating, DNA damaging, mode of action but must be due to other, nongenotoxic, mechanisms such as peroxisome proliferation, hepatomegaly, or cytotoxicity due to protein binding. The risk assessment in man and the interpretation of the carcinogenicity data for rodents are discussed.show moreshow less

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Metadaten
Author: A. von Däniken, Werner K. Lutz, C. Schlatter
URN:urn:nbn:de:bvb:20-opus-61087
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Pharmakologie und Toxikologie
Language:English
Year of Completion:1981
Source:Toxicology Letters (1981) 7, (4-5) 305-10.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
GND Keyword:Toxikologie
Release Date:2012/01/26
Licence (German):License LogoDeutsches Urheberrecht