Alpha-fetoprotein production by the synchronized regenerating murine liver. Its independence on the phases of the mitotic cycle.

DNA synthesis in the regenerating liver of mice poisoned with carbon tetrachloride (CCl4) was inhibited by infusion of hydroxyurea (HU). The infusion was started prior to the beginning of DNA synthesis and continued up to 60-72 h after CCl4 administration. The AFP-containing cells in liver were demonstrated by the immunoperoxidase technique. Phases of the cell cycle were estimated by autoradiography following the administration of [3H] thymidine. Despite the arrest of all proliferating hepatocytes at the G1-S interphase, the pattern of AFP production in the HU-infused mice was the same as in normal regeneration. Serum AFP levels rose from the 2nd up to the 3rd to 4th day after administration of CCl4 and AFP was demonstrated in a small number of hepatocytes, bordering the necrotic areas of the liver. After release from the HU block, hepatocytes synchronously entered S phase. The degree of synchronization was of the same order as the size of the hepatocyte proliferative pool in regenerating liver. AFP was found in all the phases of the mitotic cycle - from G1 to postmitotic cells indicating that there is no direct correlation between AFP production and the phases of the mitotic cycle of hepatocytes in the murine regenerating liver.