MODIFICATION OF RADIATION RESPONSE OF CHO CELLS BY METHYL-ISOBUTYL XANTHINE .1. REDUCTION OF DO

Methyl-isobutyl xanthine (MIX), an inhibitor of cyclic AMP phosphodiesterase, induces transient elevation of intracellular cyclic AMP in CHO cells when added to the medium. Reduction of D(o) of irradiated, exponentially growing CHO cells is observed when MIX is added to the medium shortly before or shortly after irradiation, or when dibutyryl cyclic AMP or prostaglandin E1 are added after irradiation. Results of the latter experiment and of experiments in which the time of MIX addition was varied in relation to the time of irradiation suggested that an important factor in reducing D(o) in MIX-treated irradiated cells was the presence of an elevated concentration of intracellular cyclic AMP after irradiation. MIX-treated cells showed reduction in survival when irradiated with high doses in late G1 and S phase, but no reduction when irradiated in early G1.