PARP-1, PARP-2, and the cellular response to low doses of ionizing radiation

Int J Radiat Oncol Biol Phys. 2004 Feb 1;58(2):410-9. doi: 10.1016/j.ijrobp.2003.09.053.


Purpose: Poly(ADP-ribose) polymerase-1 (PARP-1) is rapidly and directly activated by single-strand breaks and is required for efficient base excision repair. These properties indicate that inhibition of PARP-1 might enhance the cellular response to low doses of radiation. We tested the effect of chemical inhibition of PARP-1 on low-dose clonogenic survival in a number of cell lines and the low-dose radiation response of a PARP-1 knockout murine cell line.

Methods and materials: Clonogenic cell survival of V79-379A and CHO-K1 hamster fibroblasts, T98G and U373-MG human glioma cells, and 3T3 mouse embryo fibroblast PARP-1 knockout cells was measured using a precise flow cytometry-based plating assay. Chemical inhibitors of PARP enzymes were tested for their effect on clonogenic survival after a range of ionizing radiation doses.

Results: Chemical inhibition of PARP activity induced marked radiosensitization of V79, CHO, and exponentially growing T98G cells in the 0.05-0.3-Gy range. This effect was not seen in U373 cells or in confluent T98G populations. Low-dose radiosensitization was not apparent in PARP-1 knockout cells.

Conclusion: Low-dose radiosensitization of actively dividing tumor cells by PARP-1 inhibitors suggests that they may have a role in enhancing the efficacy of ultrafractionated or low-dose-rate radiotherapy regimens. We hypothesize that PARP-2 compensates for the absence of PARP-1 in the knockout cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / pharmacology
  • Cell Line / radiation effects
  • Cell Line, Tumor / radiation effects
  • Cell Survival*
  • Cricetinae
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Mice
  • Phenanthrenes / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Quinazolines / pharmacology
  • Radiation Dosage
  • Radiation Tolerance*
  • Radiation-Sensitizing Agents / pharmacology*
  • Tumor Stem Cell Assay


  • Benzamides
  • Enzyme Inhibitors
  • N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
  • NU 1025
  • Phenanthrenes
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Quinazolines
  • Radiation-Sensitizing Agents
  • 3-aminobenzamide