Contribution to some radiobiological aspects of the investigation of radiosensitizers of hypoxic cells. Part IV: Radiosensitizing effect of metronidazole evaluated on the level of postirradiation changes of bone marrow cellularity in rats protected by induced hypoxia of lower body half.

Radiosensitizing effect of metronidazole (Entizol, Polfa, Poland) was tested on an experimental model of ischaemized bone marrow. The changes of bone marrow cellularity were recorded after whole body irradiation of rats protected with abdomen compression during irradiation. With an increasing dose of irradiation proportional and significant decrease of nuclear elements in bone marrow occurred the third day after irradiation. Metronidazole administered to unprotected rats (without compression) did not show any effect. The abdomen compression led to a pronounced radioprotection but metronidazole administration reduced this effect significantly. Ischaemization of the lower half of rat body produced on the level of bone marrow cellularity the protection corresponding to DRF (dose reduction factor) = 1.96 the third day after irradiation. DRF value decreased to 1.52 by metronidazole application which corresponds to ER (enhancement ratio) = 1.29.

Contribution to some radiobiological aspects of the investigation of chemical radiosensitizers of hypoxic cells. Part V: Metronidazole--dependence of its radiosensitizing effect on the dose, time interval of administration and hypoxia degree of the bone marrow evaluated according to the changes of its cellularity in rats.

In the experiments on female rats of Wistar strain the effect of metronidazole (Entizol - Polfa) was studied administrated in aqueous solution with a gastric pipette into the stomach. Dependence was analyzed on the dose of metronidazole, on the time interval of administration before irradiation and on the degree of hypoxia of bone marrow during irradiation induced in the lower part of the body and graded by the abdomen compression with an inflatable rubber cuff with overpressure 4, 6.7, 13.3 and 20 kPa. The effect of whole body irradiation (60Co source) was evaluated according to the changes of bone marrow cellularity (BMC) the third day after irradiation. The sensitizing effect of metronidazole increases rapidly up to dose of 30 mg/kg with rising dose of the drug, then at higher doses only slowly. With prolonging interval of the application of 600 mg/kg body weight the sensibilization increases and reaches the peak after 1-2 hours, then it gradually decreases till the complete disappearance after 10-15 hours. In both cases irradiation was carried out at abdomen compression corresponding to 20 kPa of overpressure in the rubber cuff. The induced hypoxia of bone marrow demonstrated a significant, protective effect, corresponding to the degree of abdomen compression which was reduced by metronidazole administration in the dose of 600 mg/kg. The reduction represents one half to one third of the protective value and is proportional to the degree of induced bone marrow hypoxia during irradiation.