RELATIONSHIP BETWEEN ABERRANT DNA-REPLICATION AND LOSS OF CELL VIABILITY IN CHINESE-HAMSTER OVARY CHO-K1-CELLS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (11) , 4744-4752
Abstract
A transient block to DNA replication induces an aberrant form of DNA synthesis. The most feasible explanation for this is that the block to DNA replication results in some segments of the chromosomal DNA being replicated more than once in a single cell cycle. This form of aberrant DNA synthesis occurred following direct inhibition of DNA replication by 1-.beta.-D-arabinofuranosylcytosine or 9-.beta.-D-arabinofuranosyladenine or after indirect inhibition with cycloheximde. Mechanisms were proposed whereby this phenomenon could induce chromosome damage and cell death. Data on the relationship between this aberrant form of DNA replication and the loss of cell viability were presented. Using Chinese hamster ovary CHO-K1 cells growing as monolayer cultures, the loss of cell viability was simultaneously monitored as measured by colony formation and the relative extent of this aberrant DNA replication induced by 2-h pulses of a series of concentrations of inhibitors of DNA replication. With either direct inhibition of DNA replication with 1-.beta.-D-arabinofuranosylcytosine or with indirect inhibition with cycloheximide, pulses of inhibitor administered to Chinese hamster ovary cells at increasing concentrations induced a progressive increase in the extent of this aberrant DNA replication which paralleled the increase in cell killing.