Enhanced liver DNA synthesis in partially hepatectomized rats pretreated with 2,3,7,8-tetrachlorodibenzo- p-dioxin

Abstract

The effect of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) on liver DNA synthesis was studied in rats after a 1 3 hepatectomy. The rats were maintained on a controlled feeding schedule and were treated with 5 μg/kg of TCDD or acetone/corn oil (control). Five days after treatment a 1 3 hepatectomy was performed and at designated times thereafter liver DNA synthesis was measured by [ 3H]thymidine incorporation into DNA. The main finding was that liver DNA synthesis was increased 8- to 10-fold by TCDD over that which was observed in control rats. This increase occurred after a latency period that was appropriate for the regenerative liver DNA synthesis response. Other experiments showed that increased incorporation of thymidine in TCDD-treated rats could be blocked by hydroxyurea, an inhibitor of semiconservative DNA synthesis, and that the increased incorporation was secondary to increased DNA synthesis and not increased thymidine kinase activity. Thus, hepatocytes in TCDD-treated rats respond in a quantitatively different manner than control rats to the same proliferative signal, 1 3 hepatectomy. Liver DNA synthesis in nonhepatectomized TCDD-treated rats tended to be greater than control, but the difference was not statistically significant.