Genotoxicity of cimetidine in primary cultures of rat hepatocytes.

The genotoxicity of cimetidine was examined in the hepatocyte primary culture/DNA-repair test and by the DNA-damage/alkaline-elution assay. A dose-dependent amount of unscheduled DNA synthesis was elicited by cimetidine, whereas DNA fragmentation occurred only in hepatocytes exposed to the highest (3 mM) concentration of the drug. These findings are in contrast with the negative results previously obtained in long-term and short-term carcinogenesis assays.