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.