Effects of some non-genotoxic chemicals on DNA synthesis in rat hepatocytes.
The effect of the antihistaminic drug methapyrilene (MP) on DNA synthesis in primary cultures of rat hepatocytes has been compared with the effects of sodium phenobarbitone (PB), clofibric acid (CA), 2-acetylaminofluorene (AAF) and dimethyl sulfoxide (DMSO). The response for all chemicals was dependent on the concentration of epidermal growth factor (EGF) in the culture medium. MP at concentrations between 0.1 and 1 mum stimulated DNA synthesis. PB had a stimulatory effect on DNA synthesis at 0.5-1 mm. A greater increase in DNA synthesis was observed in the absence of EGF in the culture medium, for both chemicals. CA (0.1 mm) increased DNA synthesis in the absence of EGF and inhibited DNA synthesis at concentrations of 10 ng/ml or more. A dose-related increase in DNA synthesis with DMSO was observed in the presence of 10 ng EGF/ml. AAF did not stimulate DNA synthesis and inhibited it in the presence of 10 ng EGF/ml.
Moret
M
M
Division of Chemical Safety Evaluation, Robens Institute, University of Surrey, Guildford, Surrey GU2 5XH, UK.
Lawrence
J N
JN
Benford
D J
DJ