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 progression for the cytotoxicity of topoisomerase inhibitors as well as for their ability to induce chromosomal aberrations and sister chromatid exchange (SCE). In the present report, we have carried out experiments in CHO cells in order to study the induction of SCE by topo I and topo II inhibitors in both euchromatin and late-replicating heterochromatin, as well as the possible influence of inhibition of DNA replication or transcription on the occurrence of SCE. Treatment with the DNA synthesis inhibitor aphidicolin reduced the frequency of SCE induced by topoisomerase inhibitors in constitutive heterochromatin of the X chromosome, while the RNA synthesis inhibitor actinomycin D also had an effect on SCE induced by high doses of the topoisomerase poisons, in spite of the lack of active transcription which characterizes this heterochromatic region.