The mitogenic potential of trichloroethylene in B6C3F1 mice

Male and female B6C3F1 mice were given TCE by gavage for 10 days. No histopathologic changes in the livers from control male and female mice were found. Moderate changes around central veins were noted in male or female mice that received 1000 mg/kg/body weight TCE. Histopathological changes included an increase in cytoplasmic eosinophilic staining and apoptosis around the central veins. Mitosis and DNA synthesis were examined using incorporation of [3H]thymidine into liver cells. Incorporation of [3H]thymidine was significantly increased in the DNA of animals receiving TCE. Total liver DNA extracted from TCA-treated mice was not significantly different than those of control groups. Autoradiographic examination of liver sections showed that the incorporation of label in control animals was primarily in perisinusoidal cells. The majority of radiolabel incorporation in TCE-treated mice was found in intermediate zone cells that appeared to be mature hepatocytes. No outstanding differences in the distribution of radiolabel in the liver from male or female mice were noted. When incorporation of [3H]thymidine was quantified by enumeration of labeled hepatocytes following autoradiography, incorporation of the radiolabel into hepatocytes increased proportionally to the applied dose of TCE, but did not increase in peri-sinusoidal cells. Increased mitotic figures in intermediate zone cells resembling mature hepatocytes were found in all mice treated with TCE. These results suggest that liver cell DNA synthesis and mitosis are stimulated by TCE and that these effects may be in part responsible for transformation of liver cells in these mice.