Novobiocin, nalidixic acid, etoposide, and 4'-(9-acridinylamino)methanesulfon-m-anisidide effects on G2 and mitotic Chinese hamster ovary cell progression

Exponentially growing Chinese hamster ovary cells, exposed to inhibitors of topoisomerase II (novobiocin, nalidixic acid, etoposide, and 4'-(9-acridinylamino)methanesulfon-m-anisidide were blocked in progression through G2. The manner of recovery from the novobiocin-induced block, following drug removal, indicated that the blockade was at and before a specific point in G2 (a transition point). The transition point for novobiocin and putative transition points for nalidixic acid and 4'-(9-acridinylamino)methanesulfon-m-anisidide were about 30 min before metaphase. The transition point for nalidixic acid varied with concentration from about 70 min before metaphase, at 1 microgram/ml, to 24 min before metaphase at 15 micrograms/ml and above. The novobiocin- and nalidixic acid-induced G2 block could not be accounted for by cytotoxicity or DNA damage (detected by neutral elution). The novobiocin-induced G2 block could not be attributed to gross RNA synthesis inhibition. Progress beyond metaphase was blocked by novobiocin but not by nalidixic acid, when cells were exposed to drug concentrations which inhibited G2 cell progression. It is suggested that the progression of Chinese hamster ovary cells into but not through mitosis may require topoisomerase II.