Trichloroacetate stimulation of liver DNA synthesis in male and female mice.

Male and female B6C3F1 mice were given trichloroacetate (TCA) by gavage for 11 days. Livers from untreated male and female mice were unremarkable by histopathologic examination. In livers from mice receiving 1000 mg/kg body weight, the centrolobular hepatic cords showed slight changes, which included increased eosinophilic staining and rare apoptosis. Areas in the intermediate zone were noted where the architecture of the liver hepatic cords was subtly changed. The changes in cord architecture seemed to define nodular areas where cellular proliferation in animals treated with TCA had occurred. No histopathologic differences were noted between the livers of treated or control, male and female animals. Mitosis and DNA synthesis were examined using incorporation of [3H]thymidine into liver cells. [3H]Thymidine incorporation into extracted liver DNA of animals receiving TCA was significantly increased over controls in all treatment groups. Autoradiographic examination of liver sections showed that the incorporation of label in control animals was predominantly in peri-sinusoidal cells, whereas the majority of radiolabel incorporation in TCA-treated animals was found in intermediate zone cells that appeared to be mature hepatocytes. No outstanding differences in the distribution of radiolabel in the liver sections from male or female mice were noted. When incorporation of [3H]thymidine was quantified by enumeration of labeled liver cells following autoradiography, incorporation of the radiolabel into hepatocytes increased with the dose of TCA given but there was no increase in radiolabel in peri-sinusoidal cells. Increased mitotic figures in intermediate zone cells resembling mature hepatocytes were noted in all mice treated with TCA. These results suggest that increased DNA synthesis and mitosis may contribute tumorigenesis by TCA.