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Abrogation by Novobiocin of Cytotoxicity Due to the Topoisomerase II Inhibitor Amsacrine in Chinese Hamster Cells¹

Department of Radiology and Radiation Biology, Colorado State University, Fort Collins, Colorado 80523

Using cultured V79 Chinese hamster cells, we found that novobiocin (or 2,4-dinitrophenol) can abrogate, almost completely, the cytotoxicity due to the topoisomerase II inhibitor amsacrine (mAMSA). V79 cells were sensitive to mAMSA killing at all stages in the cell cycle but mainly in S phase followed by late G₁ phase; however, novo rescued cells of all ages.

The properties of two kinds of radiation-sensitive Chinese hamster cells were also examined, i.e., the line of V79 cells that can be rescued by caffeine, designated S-10 (H. Utsumi and M. M. Elkind, Radiat. Res., 96: 348–358, 1983); and Chinese hamster ovary cells (P. A. Jeggo and L. M. Kemp, Mutat. Res., 112: 313–327, 1983) which are also sensitive to other DNA-damaging agents. As is the case for exposure to radiation, after mAMSA treatment caffeine rescued V79/S-10 cells. Although Jeggo's Chinese hamster ovary cells were more responsive to mAMSA, novo still abrogated mAMSA toxicity in the mutant cells as well as in the parental Chinese hamster ovary cells. 2,4-Dinitrophenol acted similarly to novo with respect to mAMSA killing, but neither compound reduced the ATP content of V79 cells.

We propose that one reason for the rescue from mAMSA killing of at least S-phase cells by novo or 2,4-dinitrophenol is their ability transiently to inhibit replicative DNA synthesis.

¹ Supported by the United States Department of Health and Human Services, USPHS, via Grant CA 47497 from the National Cancer Institute.

² Present address: Radiation Biology Center, Kyoto University, Kyoto 606, Japan.

³ Present address: Department of Veterinary Radiology, Nihon University, Tokyo 154, Japan.

⁴ To whom requests for reprints should be addressed.

Received 8/ 9/89. Revised 12/ 1/89.

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