High yield of endoreduplication induced by ICRF-193:: a topoisomerase II catalytic inhibitor

An uncommonly high yield of spontaneous endoreduplication is a feature of the CHO mutant EM9, besides its defective repair of single, as well as double-DNA strand-breaks and its extraordinarily elevated yield of sister chromatid exchanges (SCEs) after bromodeoxyuridine (BrdU) incorporation into DNA. Since the nuclear enzyme topoisomerase II (topo II) has been reported to be responsible for the segregation of daughter chromosomes during mitosis, in the present investigation we have made use of the bisdioxopiperazine ICRF-193, a topo II catalytic inhibitor that interferes with the normal turnover of the enzyme. In order to see whether both EM9 cells and its parental cell line AA8, which show differences in the spontaneous frequency of endoreduplicated cells are or not equally sensitive to the topo II catalytic inhibitor, both cell lines have been treated with a range of doses of the bisdioxopiperazine. Our results show that both cell lines respond to the treatment entering in an endoreduplication cycle, but the EM9 cells are extremely sensitive to the inhibition of topo II. (C) 2002 Elsevier Science B.V. All rights reserved.