Cytogenetic effects of inhibition of topoisomerase I or II activities in the CHO mutant EM9 and its parental line AA8.

The possible relationship between topoisomerase activities and the occurrence of SCE and chromosomal aberrations was investigated in the CHO ethyl methanesulfonate-sensitive mutant EM9 and its parental line, AA8. The Topo II inhibitor m-AMSA induced fewer SCE in EM9 than in AA8, mainly when given during the first S period. When the Topo I inhibitor camptothecin was used, it showed a higher efficiency to induce both chromosomal aberrations and SCE in EM9 than in AA8. The impact of BrdU incorporated into parental DNA on topoisomerase activity was tested using nuclear extracts from both EM9 and AA8 assayed for their ability to decatenate kinetoplast DNA by Topo II and to relax supercoiled plasmid DNA by Topo I. Taken as a whole, the results seem to indicate that there are differences between the two cell lines, consistent with the hypothesis put forward by other investigators that topoisomerases are involved in the molecular mechanism of SCE.