Histopathological effects of methotrexate on mouse liver.

Mice were injected with up to 9 doses of methotrexate and killed at intervals after treatment. Liver changes were assessed histopathologically and by image analysis, and included vacuolation and ballooning degeneration of centrilobular liver cells. There was considerable irregularity in nuclear size in methotrexate-treated mice, in which hepatic nuclei were significantly larger than those of control animals. Fatty change was not induced in the liver by these doses of methotrexate, and there was no cellular infiltration or fibrosis.