The evaluation of erythrocyte membrane response to combined treatment of radiation and nitroimidazoles.

The effect of gamma-irradiation on human erythrocytes in the presence of nitroimidazoles in aerobic conditions was investigated. It was found that both 1-(2-nitroimidazole-1-y1)-3-methoxy-2-propanol (misonidazole, MISO) and 1-(2-methyl-4,5-dinitroimidazoyle)-3-chloro-2-hydroxypropane (4,5-NO2) inhibited membrane-bound ATPase activity without irradiation. Treatment with 4,5-NO2 enhanced the radiation-induced decrease in the activity, whereas irradiation after treatment of membranes with MISO had a variable, concentration-dependent effect. Irradiation of cells in the presence of MISO concentrations less than 34 micrograms/ml decreased reduced glutathione (GSH) levels and increased malondialdehyde (MDA) formation. With the same concentrations a marked oxidative effect of 4,5-NO2 was observed. Significant correlations between 4,5-NO2 concentrations, GSH levels and lipid peroxidation, and also between GSH and MDA levels, were observed. Increasing radiation doses decreased erythrocyte membrane sensitivity to the stabilizing effect of unsaturated fatty acids. This effect for oleic acid was elevated by 4,5-NO2 and suppressed by GSH and BHT. Therefore, it is concluded that in aerobic conditions the red blood cell membrane is a target to radiation and to hypoxic cell radiosensitizers.