Cell cycle perturbations following DNA damage in the presence of ADP-ribosylation inhibitors

Abstract

Cell cycle analysis by DNA flow cytofluorimetry and auto-radiography has been utilized to investigate the effects of 3-methoxybenzamlde (MBA), a potent inhibitor of ADP ribosylation reactions, on cell cycle progression in N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-treated C3H10T1/2 cells. Following a dose of 6.8 μM MNNG, the presence of MBA resulted in an increased length of S phase from ∽6.5 h to 10 h and in an accumulation of cells in G₂ with a mitosis delay of 12 h. Progression to the next S phase occurred 5–10 times more slowly and the cells ultimately accumulated in G₂ Increasing the dose of MNNG resulted in a complete block in cell division in the absence of ADP ribosylation. These results suggest that ADP-ribosylation reactions, which do not seem to be necessary for DNA excision repair in nondividing cells, are essential for co-ordinating the events of DNA excision repair with DNA replication and events related to progression through the cell cycle.