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Cellular Retention of 9-ß-D-Arabinofuranosyladenine 5'-Triphosphate and the Pattern of Recovery of DNA Synthesis in Chinese Hamster Ovary Cells¹

Department of Chemotherapy Research, The University of Texas, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030

The factors associated with the recovery of DNA synthesis in Chinese hamster ovary cells after inhibition with 9-ß-D-arabinofuranosyladenine have been investigated. Maintenance of cellular concentrations of the active metabolite 9-ß-D-arabinofuranosyladenine 5'-triphosphate was dependent upon a constant exogenous source of 9-ß-D-arabinofuranosyladenine, without which the triphosphate rapidly degraded. DNA synthesis was inhibited maximally at cellular concentrations of 9-ß-D-arabinofuranosyladenine 5'-triphosphate in excess of 100 µM, but it recovered substantially as the triphosphate concentrations declined below 30 µM. Autoradiographic studies indicated that 9-ß-D-arabinofuranosyladenine had a synchronizing effect on the cells and that recovery of DNA synthesis occurred initially at rates much reduced from those seen in uninhibited cells. A greater portion of an inhibited population recovered DNA synthesis than was able to retain clonogenic potential. These results are consistent with a mechanism of toxicity that postulates recovery of DNA synthesis as a requisite for the loss of viability.

¹ Supported by American Cancer Society Grant CH-130 and Grant CA28596 from the National Cancer Institute, Department of Health and Human Services.

² Recipient of a Rosalie B. Hite predoctoral fellowship. Present address: Simpson Memorial Institute, University of Michigan Medical School, Ann Arbor, MI 48109.

³ To whom requests for reprints should be addressed, at Department of Chemotherapy Research, Box 52, The University of Texas, M. D. Anderson Hospital and Tumor Institute, 6723 Bertner Ave., Houston, TX 77030.

Received 4/29/85. Revised 12/13/85. Accepted 12/18/85.