INCREASED LEVELS OF DNA TOPOISOMERASES IN CULTURED CHO CELLS TREATED WITH THE ANTITUMOUR DRUG 5-AZACYTIDINE

Cultured Chinese hamster ovary (CHO) cells were treated with the cytidine analogue 5-azacytidine (5-azaC) which, in good agreement with results previously described from studies carried out in other primary or established mammalian cell lines, resulted in extensive chromosome decondensation and a shift in the time of replication of normally late-replicating heterochromatin to earlier replication. DNA topoisomerases (mainly topo I) have been involved in transcription, and the hypomethylating effect of 5-azaC reportedly results in the expression of silenced genes. Whether such an increase in transcription is paralleled by increased levels of both topo I and topo II, as well as by an enhancement in the topoisomerase activities, has been investigated in this work. The results seem to suggest that both the relative amount of topoisomerases and their activities are enhanced after a protracted treatment with the cytidine analogue over those observed in untreated controls. These observations could be significant for antitumour therapy.