Stimulation of hepatocellular proliferation by a serum factor from thioacetamide-treated rats

Rats treated with thioacetamide undergo hepatocellular proliferation reminscent of liver regeneration following partial hepatectomy. 36 h after administration of 50 mg thioacetamide/kg body weight to rats, [3H]thymidine incorporation into hepatic DNA reaches a peak of 78-10(3) dpm/mg DNA compared to a control of 3.2-10(3) dpm/mg DNA. Serum obtained from 6 to 48 h after administration of thioacetamide to rats stimulated hepatic but not kidney DNA synthesis in mice and rats. Autoradiography revealed an increase in the incorporation of labelled thymidine into the nuclei of mouse hepatocytes. The mitotic index of the liver was also increased. The serum factor stimulating these changes in the liver was non-dialyzable and heat stable. These results indicate that thioacetamide induced liver injury results in a humoral factor which stimulates DNA synthesis in rat and mouse identified in the serum from partially hepatectomized rats.