The Evaluation of Erythrocyte Membrane Response to Combined Treatment of Radiation and Nitroimidazoles

Summary

The effect of γ-irradiation on human erythrocytes in the presence of nitroimidazoles in aerobic conditions was investigated. It was found that both 1-(2-nitroimidazol-1-y1)-3-methoxy-2-propanol (misonidazole, MISO) and 1-(2-methyl-4,5-dinitroimidazolyl)-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 > 34 μg/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.