Effect of aphidicolin on DNA synthesis, PLD-recovery and DNA repair of human diploid fibroblasts.
The effect of aphidicolin, a specific inhibitor of DNA polymerases alpha and delta, was studied on DNA synthesis, PLD-recovery and DNA double-strand break rejoining in X-irradiated human fibroblasts. In unirradiated, exponentially growing cells, aphidicolin (0.5-5 micrograms ml) inhibited DNA synthesis almost completely. This effect depended not only on aphidicolin concentration but also on the duration of pre-incubation. The action of aphidicolin was found to be reversible. When aphidicolin had been removed, colony forming ability was not affected in aphidicolin pretreated cells. Aphidicolin pretreated and irradiated cells showed a reduction in PLD-recovery, dependent on aphidicolin concentration and duration of pretreatment. The initial number of DNA double-strand breaks (calibrated by 125I decay) was not affected by aphidicolin. However, after incubation for 90 min in the presence of aphidicolin there was a large reduction in double-strand break rejoining. With long incubation periods in aphidicolin rejoining was almost completely inhibited.
Institut für Strahlenbiologie, Bonn, Germany.
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Baumstark-Khan
D000328:Adult; D016590:Aphidicolin / Q000494:pharmacology*; D002470:Cell Survival / Q000528:radiation effects; D004247:DNA / Q000096:biosynthesis*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans
D016590:Aphidicolin; D004247:DNA