Killing and Mutation of Density Inhibited V-79 Cells as Affected by Inhibition of Poly(ADP-Ribose) Synthesis

Abstract

It is now established that the synthesis of poly(ADP-ribose) is stimulated following DNA-damage (1–4). Inhibition of that enhanced synthesis has been found to increase cellular cytotoxicity depending upon the damaging agent; in some cases, inhibition enhances the effect, whereas, in other cases, it is of no apparent consequence. Amongst the first group are N-methyl-N′- nitro-N-nitrosoguanidine (5, 6) and H₂O₂ (7) and in the second, X-rays and UV light (6). It seemed that there was no general role for poly(ADP-ribose) in repair activity, although various suggestions regarding its involvement in repair had been made. It was clear that so far as normally growing mammalian cells were concerned, the role of poly(ADP-ribose) in repair remains yet to be clarified. Mammalian cells in a density-inhibited condition has been considered to be equivalent to cells in a tumor (8). It is of interest to see if cells in the density inhibited condition would behave in the same way as exponentially growing cells to inhibition of poly(ADP-ribose) synthesis following exposures to X-rays, UV light and H₂O₂, representing DNA damaging agents of group 1 and 2. It is expected that these results might lead to some clarification of the situation.