Testing the SCE mechanism with non-poisoning topoisomerase II inhibitors

There are controversial theoretical models about a possible involvement of DNA topoisomerase II (topo II) in the molecular mechanism of sister chromatid exchanges (SCEs). In order to clarify the role of this enzyme, if any, in such recombinational event, CHO parental AA8 and mutant EM9 cells, which shows and extremely high baseline frequency of SCE, have been treated with different doses of the non-poisoning topoisomerase inhibitors, ICRF-193 and bufalin. The frequencies of SCEs after the treatments have been determined and the inhibitory effect of these compounds has been assessed using a topo II activity assay. The results indicate that ICRF-193 and bufalin effectively inhibit topo II activity in AA8 and EM9 cell lines. ICRF-193 induced a moderate increase in the frequency of SCEs in both types of cells, while bufalin did not modify the level of SCEs in any of them. The results are discussed taking into account the apparently unlike mechanisms of inhibition of topo II by ICRF-193 and bufalin. (C) 2001 Elsevier Science B.V. All rights reserved.