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Novobiocin, Nalidixic Acid, Etoposide, and 4'-(9-Acridinylamino)methanesulfon-m-anisidide Effects on G₂ and Mitotic Chinese Hamster Ovary Cell Progression¹

Experimental Oncology, Department of Radiology, University of Utah Medical Center, Salt Lake City, Utah 84132

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 µg/ml, to 24 min before metaphase at 15 µg/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.

¹ This investigation was supported by USPHS Grant CA 40245 awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed.

Received 7/15/88. Revised 2/14/89. Revised 4/25/89. Accepted 5/25/89.

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