Radiation response of NIH/3T3 mouse fibroblasts overexpressing human poly(adenosine diphosphate ribose) polymerase

Poly(adenosine diphosphate ribose) [poly(ADP‐ribose)] polymerase is a mammalian enzyme which synthesizes long chains of ADP‐ribose attached to various nuclear proteins in response to DNA strand breaks. A role for this enzyme in cellular radioresistance has been postulated due to the radiosensitizing effect of chemical inhibitors of the enzyme on some cell lines. Inhibitor studies, however, lack specificity and direct evidence for involvement of the enzyme in radioresistance is still needed. In experiments described here, intracellular levels of the enzyme were modulated using vectors to express sense and antisense human cDNA transcripts of poly(ADP‐ribose) polymerase in stably transfected NIH/3T3 mouse fibroblasts. Although antisense constructs failed to lower enzyme levels, sense transcripts increased enzyme levels. None of the transfectants, however, showed any difference in either radiation sensitivity or DNA strand break repair rates. These results suggest that simple elevation of poly(ADP‐ribose) polymerase does not affect the intrinsic cellular radioresistance of these cells. © 1993 Wiley‐Liss, Inc.