Cellular retention of 9-beta-D-arabinofuranosyladenine 5'-triphosphate and the pattern of recovery of DNA synthesis in Chinese hamster ovary cells.
The factors associated with the recovery of DNA synthesis in Chinese hamster ovary cells after inhibition with 9-beta-D-arabinofuranosyladenine have been investigated. Maintenance of cellular concentrations of the active metabolite 9-beta-D-arabinofuranosyladenine 5'-triphosphate was dependent upon a constant exogenous source of 9-beta-D-arabinofuranosyladenine, without which the triphosphate rapidly degraded. DNA synthesis was inhibited maximally at cellular concentrations of 9-beta-D-arabinofuranosyladenine 5'-triphosphate in excess of 100 microM, but it recovered substantially as the triphosphate concentrations declined below 30 microM. Autoradiographic studies indicated that 9-beta-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.
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Shewach
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Plunkett
D000818:Animals; D001088:Arabinonucleotides / Q000378:metabolism*; D001345:Autoradiography; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis*; D005260:Female; D010053:Ovary / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014740:Vidarabine / Q000494:pharmacology*; D001084:Vidarabine Phosphate / Q000031:analogs & derivatives / Q000378:metabolism*
D001088:Arabinonucleotides; D014316:Tritium; D001084:Vidarabine Phosphate; C000101:ara-ATP; D004247:DNA; D014740:Vidarabine; D013936:Thymidine