Fulltext

Nafenopin-induced rat liver peroxisome proliferation reduces DNA methylation by N-nitrosodimethylamine in vivo

Wiestler, Otmar D. ; Schmerold, Ivo ; Fringes, Birgitta ; Volk, Benedikt ; Kleihues, Paul

In: Carcinogenesis, 1985, vol. 6, no. 9, p. 1309-1313

Ajouter à la liste personnelle
    Titre
    • Nafenopin-induced rat liver peroxisome proliferation reduces DNA methylation by N-nitrosodimethylamine in vivo
    Auteur
    • Wiestler, Otmar D.. Laboratory of Neuropathology, Institute of Pathology, University of Freiburg, Albertstrasse 19, D-7800 Freiburg im Breisgau, D-8000 Munchen 22, FRG, CH-8091 Zūrich, Switzerland
    • Schmerold, Ivo. Institute of Pharmacology, Toxicology and Pharmacy, Faculty of Veterinary Medicine, University of Munich D-8000 Munchen 22, FRG
    • Fringes, Birgitta. Laboratory of Neuropathology, Institute of Pathology, University of Freiburg Albertstrasse 19, D-7800 Freiburg im Breisgau
    • Volk, Benedikt. Laboratory of Neuropathology, Institute of Pathology, University of Freiburg Albertstrasse 19, D-7800 Freiburg im Breisgau
    • Kleihues, Paul. Laboratory of Neuropathology, Institute of Pathology, University of Zürich CH-8091 Zūrich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Carcinogenesis, 1985, vol. 6, no. 9, p. 1309-1313. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:301203
    Summary
    The hypolipidaemic drug nafenopin (NAF) has been shown to enhance the hepatocarcinogenic effect of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine in rats. We have investigated whether the NAF-induced peroxisome proliferation in hepatocytes interferes with NDMA's metabolism and interaction with DNA. Adult male Wistar rats received a single i.p. injection of [14C]NDMA (2 mg/kg) and were killed 4 h later. DNA was isolated from liver and kidney, hydrolysed in 0.1 N HCI and analysed by Sephasorb chromatography. In rats pre-treated with NAF (0.2% in the diet over a period of 3 weeks), the concentration of N7-methylguanine in hepatic DNA (μmol/mol guanine) was 46% below control values. This is probably due to the greater amount of target DNA, as NAF caused a marked hepatomegaly with a 50% increase in total liver DNA content. Concentrations of N7-methylguanine in kidney DNA were twice as high in NAF-pre-treated animals when compared to control rats. This is unlikely to result from a shift in the metabolism of NDMA from liver to other rat tissues since the time course and extent of the conversion of [14C]NDMA to 14CO2 and 14C-labelled urinary metabolites were identical in NAF-treated and control animals. There was no indication that NAF inhibits the activity of the hepatic O6-alkylguanine-DNA alkyltransferase