Effects of Aphidicolin on Cell Proliferation, Repair of Potentially Lethal Damage and Repair of DNA Strand Breaks in Ehrlich Ascites Tumour Cells Exposed to X-rays

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Abstract
The effects of aphidicolin, a specific inhibitor of DNA .alpha.-polymerase, were studied on various cellular end-points and on DNA strand break repair. In the concentration range 0.02-2 .mu.g/ml DNA synthesis was strongly inhibited, resulting in a concomitant loss of cell proliferation ability; RNA and protein synthesis were unaffected in this range. At these concentrations PLD [potentially lethal damage] repair in X-irradiated plateau-phase cells was unaffected even after 7 h treatment with aphidicolin; however, at higher concentrations (> 2 .mu.g/ml) PLD repair was inhibited. In the low concentration range (< 2 .mu.g/ml) PLD repair can be seen in exponentially growing cells; and, from experiments with synchronized cells, it was established that the PLD repair observed can be attributed to the S-phase population, the survival of G1-cells not being affected by aphidicolin. The promotion of PLD repair in exponentially growing cells was in excess of that observed for the same cells in balanced salt solution in which PLD repair is usually observed. At high concentrations (> 2 .mu.g/ml) of aphidicolin, both X-irradiated and control S-cells were killed increasingly as concentration increased. The repair of DNA strand breaks (single and double) was unaffected in the low concentration range, but a strong inhibition was observed at high concentration. .alpha.-Polymerase, which is strongly inhibited at low concentrations of aphidicolin as evidenced by the inhibition of DNA synthesis, plays no major part in the repair of DNA strand breaks or in the repair of PLD.

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