Poly(ADP-Ribose) Synthetase Inhibitor Effects on Cellular Functions

  • William R. Kidwell
  • Philip D. Noguchi
  • Michael R. Purnell
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)

Abstract

The original report that certain poly(ADP-ribose) synthetase inhibitors block the repair of DNA chain breaks [1] has been confirmed by a number of laboratories [2–4]. In spite of this, a systematic approach to answering the fundamental question of whether synthetase plays an obligatory role in the repair process has not been undertaken. We have attempted to evaluate this possibility by comparing the potency of six synthetase inhibitors for inhibiting synthetase and for blocking the repair of γ-ray-induced DNA chain breaks. The results of this analysis were decidely mixed — some inhibitors being more portent in blocking repair than predicted on the basis of their Ki for synthetase and some being less effective than anticipated. Consequently, assays were made of the potency of the inhibitors for reducing cell viability or for affecting RNA synthesis. Cell viability was reduced by the synthetase inhibitors in direct relationship to their potency as synthetase inhibitors, with one exception. The effects of the inhibitors on the uptake of RNA precursors were, however, not related to their Ki’s for synthetase.

Keywords

Sedimentation Thymidine Triphosphate Nicotinamide Uridine 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • William R. Kidwell
    • 1
  • Philip D. Noguchi
    • 2
  • Michael R. Purnell
    • 3
  1. 1.Laboratory of PathophysiologyNational Cancer InstituteBethesdaUSA
  2. 2.Cell Biology Branch, FDANIHBethesdaUSA
  3. 3.Cancer Research UnitThe Royal Victoria InfirmaryNewcastle upon TyneGreat Britain

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