Changes in DNA synthesis circadian rhythms in a hepatocellular carcinoma after hepatectomy

Abstract

The effect of partial hepatectomy on the DNA synthesis rhythms of ES12a hepatocellular carcinoma grafted into C3H/S male mice was studied and compared with tumor growth in unoperated animal controls. The subtotal hepatectomy also changes the concentration of substances related to cellular proliferation to generate a compensatory hyperplasia in the liver. Thus, we analyzed the interaction between liver regeneration after hepatectomy and the DNA synthesis activity of the tumor. The animals were sacrificed every 4 h throughout one complete circadian cycle. All experimental groups of animals received an intraperitoneal dose of 50 mg of 5-bromodeoxiuridine per kg of body weight before being killed. Tumor samples were processed for histology and immunohistochemistry. DNA synthesis indices were expressed as labeled nuclei per 1000 nuclei. The results show that the ES12a tumor displays the DNA synthesis activity rhythm which, as in normal hepatocytes, passes through a peak during the nocturnal phase, and the surgery alters the temporal structure of the DNA synthesis indices. This fact should be considered in both neoplastic drug treatments and in growth related experiments.