The Effect That 2,3,7,8-Tetrachlorodibezo-p-dioxin Has on Rat Liver DNA Synthesis

Abstract

The influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on rat liver DNA synthesis was studied in rats after particular challenges: partial hepatectomy. chalone treatment, or starvation. The rats were maintained on a controlled feeding and lighting schedule and treated with a single oral dose of 5 ug/kg of TCDD or acetone/corn oil (control). Five days after treatment, rats were given their respective challenge, and 24-28 hours later when the DNA synthesis reached a peak, liver DNA synthesis was measured by 3H thymidine incorporation. Main findings were that liver DNA synthesis was: increased 2-3 fold by TCDD in rats challenged by 1/3 partial hepatectomy, decreased the same amount by chalone treatment in TCDD treated and control rats, and showed no significant difference in DNA synthesis between TCDD and control animals in the starvation or non-challenged experiments. The overshoot in DNA synthesis seen in the 1/3 hepatectomized animals pretreated with TCDD, occurred after a latency period that was appropriate for the regenerative liver DNA response. The significance of this finding is that it shows that liver cells in TODD treated rats respond in a quantitatively different manner to the 1/3 hepatectomy (a prolifferative signal), than do control liver cells. The chalone results are significant, in that they show that TCDD does not reduce the cells receptivity to chalone. In combination with initiation/promotion results of other researchers, these results may ultimately provide insight into the mechanisms of action of TCDD as a liver tumor promoter.