Poly(ADP-Ribose) Synthetase Inhibitor Effects on Cellular Functions
The original report that certain poly(ADP-ribose) synthetase inhibitors block the repair of DNA chain breaks  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.
KeywordsEpidermal Growth Factor Reduce Cell Viability Repair Rate Cloning Efficiency Synthetase Inhibitor
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