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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 1985

AutorInnen: Wiestler, OD; Schmerold, I; Fringes, B; Volk, B; Kleihues, P

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

Quelle: Carcinogenesis. 1985; 6(9):1309-1313



Autor/innen der Vetmeduni Vienna:

Schmerold Ivo

Beteiligte Vetmed-Organisationseinheiten
Institut für Pharmakologie und Toxikologie


Abstract:
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 HCl 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 (mumol/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.

Keywords Pubmed: Animals
Cell Division/drug effects
DNA/metabolism*
Dimethylnitrosamine/metabolism*
Liver/drug effects*
Liver/metabolism
Liver Neoplasms, Experimental/chemically induced
Male
Methylation
Microbodies/drug effects*
Nafenopin/toxicity*
Propionates/toxicity*
Rats
Rats, Inbred Strains


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