Effect of poly(adenosinediphosphoribose) synthesis inhibitors and structurally related compounds on radiation-induced...

A variety of poly(adenosinediphosphoribose) p(ADPR) synthesis inhibitors, structurally related compounds with no inhibitory activity, and agents which reduce radiation-induced G2 arrest, were tested for the concentration dependence of their effect on (a) CHO cell progression to mitosis, (b) the duration of G2 arrest in X-irradiated CHO cells and (c) [14C]NAD incorporation in permeabilized CHO cells, as a measure of p(ADPR) synthetase activity. Caffeine and nicotinamide uptake by viable cells was also measured. The concentration dependencies for reduction of radiation-induced G2 arrest and for p(ADPR) synthesis inhibition were markedly disparate, although all of the active inhibitors of p(ADPR) synthesis did reduce the duration of radiation-induced G2 arrest to some extent. These data indicate that p(ADPR) synthesis is not a requirement for the induction of G2 arrest by ionizing radiation.