THE REGULATION OF DNA-REPAIR PROCESSES IN MAMMALIAN-CELL .4. THE ROLE OF DNA-POLYMERASES IN THE REGULATION OF THE REPAIR OF IONIZING RADIATION-INDUCED DNA SINGLE-STRAND BREAKS BY THE EPIDERMAL GROWTH-FACTOR

A study was made of the repair of ionizing radiation-induced DNA single-strand breaks (SSB) in proliferating and quiescent mouse Swiss 3T6 cells and in those stimulated from the quiet status by epidermal growth factor in combiation with insulin, in the presence of specific inhibitors of DNA polymerase a and delta (aphidicolin) and DNA polymerase beta (2', 3'-dideoxythymidine-5'-triphosphate). The repair of DNA SSB induced by X-ray-irradiation (10 Gr) or by gamma-ray irradiation (150 Gr) is more sensitive to aphidicolin independently of cell proliferating status. Aphidicolin inhibits the recovery of single-strand DNA in quiescent and mitogen-stimulated cells three times stronger than in proliferating cells. The influence of 2', 3'-dideoxythymidine-5'-triphosphate on the rate of DNA SSB repair in cells of all the three types does not differ. Thus, the decrease in DNA repair efficiency in quiescent cells is connected with a decrease in the activity of aphidicolin-sensitive DNA polymerase, apparently DNA polymerase alpha. It is suggested that the regulation action of mitogens on the DNA SSB repair may be determined by qualitative changes of this enzyme or of some conditions in which it functions. The involvement of DNA polymerase delta in this process is not excluded.