Inhibition of Gamma-Ray Dose-Rate Effects by D 2 O and Inhibitors of Poly(ADP-Ribose) Synthetase in Cultured Mammalian L5178Y Cells

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Abstract
Effects of deuterium oxide (D2) and 3-aminobenzamide, an inhibitor of poly(ADP-ribose) synthetase, on cell proliferation and survival were studied in cultured mammalian [mouse lymphocytic leukemia] L5178Y cells under growing conditions and after acute and low-dose-rate irradiation at about 0.1-0.4 Gy[gray]/h of .gamma. rays. Growth of irradiated and unirradiated cells was inhibited by 45% D2O but not by 3-aminobenzamide at 10 mM, except for treatments > 30 h. The presence of these agents either alone or in combination during irradiation at low dose rates suppressed almost totally the decrease in cell killing due to the decrease in dose rate. The D2O did not inhibit the radiation-induced increase in poly(ADP-ribose) synthesis as measured by the incorporation of [14C]NAD into the acid insoluble fraction, contrary to 3-aminobenzamide. Among other inhibitors tested, theobromine and theophylline were found to be effective in eliminating the dose-rate effects of .gamma. rays. Possible mechanisms underlying the inhibition are discussed.