Effects of aphidicolin on repair replication and induced chromosomal aberrations in mammalian cells

The influence of aphidicolin, an inhibitor of polymerase alpha, on UV-induced repair replication in human skin fibroblasts, as well as in HeLa cells, was determined. In growing fibroblasts and in HeLa cells, aphidicolin had a potentiating effect on UV-induced repair replication, whereas in fibroblasts grown to confluency, aphidicolin had an inhibitory effect. This inhibitory effect was stronger when measured in the presence of hydroxyurea. In HeLa cells the presence of both aphidicolin and hydroxyurea also had an inhibitory effect, but in the presence of hydroxyurea alone, UV-induced repair replication was enhanced. The results of these studies can be explained on the basis of differences in deoxyribonucleotide triphosphate pool sizes in growing and confluent cells. Post-treatment of X-irradiated human lymphocytes in the G0 and G1 stages with aphidicolin increased the frequencies of X-ray-induced chromosomal aberrations. Such an increase was not observed in G1 cells of CHO after similar treatment with X-rays and aphidicolin. However, treatment with aphidicolin, in the G2 stage, of CHO cells that had been exposed to UV or alkylating agents in the G1 stage increased the frequencies of induced chromatid breaks. The significance of these results is discussed.