SISTER-CHROMATID EXCHANGE INDUCED BY DNA TOPOISOMERASES POISONS IN LATE REPLICATING HETEROCHROMATIN - INFLUENCE OF INHIBITION OF REPLICATION AND TRANSCRIPTION

Previous studies have shown the importance of DNA replication fork pro gression for the cytotoxicity of topoisomerase inhibitors as well as f or their ability to induce chromosomal aberrations and sister chromati d exchange (SCE). In the present report, we have carried out experimen ts in CHO cells in order to study the induction of SCE by topo I and t opo II inhibitors in both euchromatin and late-replicating heterochrom atin, as well as the possible influence of inhibition of DNA replicati on or transcription on the occurrence of SCE. Treatment with the DNA s ynthesis inhibitor aphidicolin reduced the frequency of SCE induced by topoisomerase inhibitors in constitutive heterochromatin of the X chr omosome, while the RNA synthesis inhibitor actinomycin D also had an e ffect on SCE induced by high doses of the topoisomerase poisons, in sp ite of the lack of active transcription which characterizes this heter ochromatic region.