Simple detection of in vivo genotoxicity of pyrimethamine in rodents by the modified alkaline single-cell gel electrophoresis assay.

Abstract We tested the genotoxicity of pyrimethamine in 5 mouse and rat organs (liver, lung, kidney, spleen, and bone marrow) using a modified alkaline single-cell gel electrophoresis (SCG) (Comet) assay. Mice and rats were sacrificed 1, 3, 6, and 24 h after oral administration of the drug at 50 and 120 mg/kg, respectively. Nuclei were isolated from each tissue and evaluated for DNA migration. Pyrimethamine induced DNA damage in cells of the liver, kidney, and lung in both species. For mice, DNA damage persisted in the liver for 24 h, while it peaked in the lung and kidney at 6 and 24 h, respectively. For rats, DNA damage in the liver peaked at 1 h and returned to almost control level at 24 h. Genotoxicity in the spleen was only observed in mice. Our results suggest that the SCG technique, using isolated nuclei can be applied to rats and mice and that the optimal sampling time is different for different organs and species.