Аннотация:Poly(ADP-ribose) polymerase (Parp) inhibitor 3-aminobenzamide (3-AB) pretreatment suppresses G1 arrest and enhances G2 arrest after gamma-irradiation in mouse embryonic fibroblast C3D2F1 3T3-a cells.3-AB partially inhibits Waf1/Cip1/p21 and Mdm2 mRNA inductions, which are transcriptionally activated by p53, suggesting that poly(ADP-ribosylation) is involved in the downstream of p53 dependent signal transduction after gamma-irradiation in C3D2F1 3T3-a cells.In this study we further examined the involvement of poly(ADP-ribosylation) in cell cycle arrest.Effect on G1 arrest suppression was lost when 3-AB was added 6 hrs after irradiation.When C3D2F1 3T3-a cells were synchronized by serum starvation, and gamma-irradiated, the peak time of DNA synthesis was not changed but the ratio of DNA synthesis was decreased in gamma-irradiated cells, where 3-AB pretreatment slightly enhanced the decrease of this ratio.3-AB decreased G1 arrest in mouse embryonic fibroblast Swiss3T3 cells dose-independent manner whereas G1 arrest was not affected at low doses in FM3A and NRF49F cells.To confirm the inhibitory effect of 3-AB on Parp activity, NAD level change was measured after gamma-irradiation.We observed NAD decrease induced by gamma-irradiation was prevented by the 4 mM 3-AB, suggesting sufficient inhibition of cellular Parp activity at 4 mM concentration.These results suggested that the effect of Parp inhibitor on G1 arrest after gamma-irradiation depends on cell phenotypes.
