RADIOPROTECTIVE EFFICACY OF DIPYRIDAMOLE AND AMP COMBINATION IN FRACTIONATED RADIATION REGIMEN, AND ITS DEPENDENCE ON THE TIME OF ADMINISTRATION OF THE DRUGS PRIOR TO IRRADIATION

We have recently demonstrated that the combined administration of dipy ridamole and adenosine monophospate to mice induces radioprotective ef fects in terms of postirradiation haemopoietic recovery in animals irr adiated with a single dose. The aim of the present experiments was to investigate the radioprotective ability of the drug combination under conditions of fractionated radiation treatment. It has been shown that administration of drugs either 15 or 60 min before each of the five d aily 3-Gy doses of gamma-radiation enhances haemopoietic recovery and survival of mice exposed to an additional ''top-up'' dose of 3.5 Gy. F urthermore, it has been ascertained that the regimen using administrat ion of the drugs 60 min prior to irradiation is more effective than ad ministration of the drugs 15 min prior to irradiation. Due to the evid ence that administration of the drugs 15 min prior to irradiation prot ects the organism mainly via mechanisms of systemic hypoxia while the pretreatment 60 min before irradiation avoids the role of hypoxia and mainly induces cell proliferation effects, our results suggest a more effective protective role of mechanisms stimulating haemopoiesis under conditions of fractionated radiation. The data may provide a basis fo r more rational use of radioprotection in fractionated radiation regim ens.