DNA topoisomerase I activity in regenerating liver of hypothyroid rats

DNA topoisomerase I activity is known to be inhibited by poly(ADP-ribosyl)ation. Both poly(ADP-ribose)polymerase and DNA topoisomerase I participate to major biological events, such as DNA transcription, repair and synthesis. Previously, a 2-fold increase in PARP activity has been shown in hypothyroid animals. Using the regenerating rat liver model, we have studied the behaviour of DNA topoisomerase I activity in hypothyroid rats. PARP activity, was also studied in another set of experiments. DNA topoisomerase I relaxing activity was determined on supercoiled plasmid DNA, and topoisomers separated by agarose gel electrophoresis. An increase in the relaxing activity of Topo I was observed early after hepatectomy. This enhancement well correlates with the reported inhibition of PARP activity at the scheduled times. The data from hypothyroid animals support an inverse relationship between PARP and Topo I. These results are completely reversed with respect to those obtained during liver regeneration in euthyroids.