Cell Cycle Dependence of Sister Chromatid Exchange Induction by DNA Topoisomerase II Inhibitors in Chinese Hamster V79 Cells1

The cell cycle dependence of sister chromai id exchange (SCE) induced by topoisomerase II inhibitors was studied in Chinese hamster V79 cells. 4'-(•>-Amu inylami110)1111-1 liansulfon-m-anisid ide, which increases the concentration of covalently linked DNA-topoisomerase II complexes (cleavable complexes), induces SCE strongly in only a short period of the cell cycle. The sensitive period was identified as occurring in early to mid-S phase through the use of labeled thymidine incorporation and flow cytometry. Novobiocin, an inhibitor which prevents formation of the cleavable complex, did not induce SCEs in any part of the cell cycle. However, novobiocin did decrease the level of 4'-(9-acridin\lamino)methansulfon-m-anisidide-induced SCEs. These results indicate that the cleavable complex may be important in 4'-(9-acridinylamino)melhansulfon-m-anisidide-induced SCE.