Protection against X-irradiation by Sulphydryl Compounds

Abstract

The radioprotective effect of 8 thiol compounds with pK-values of their thiol groups varying from 8.5-10.8 was tested on isolated cells in vitro. The influence of variations in pH of the incubation medium between 6.3 and 8.3 was investigated. The ability of the cells to form colonies was used as the criterion for survival. By comparing the protection affected by different concentrations of the various compounds it was found that a good correlation existed between the degree of radio-protection and the thiolate concentration in the medium. This correlation was also found to be present under anoxic conditions. It was concluded that the increase of the radio-protective activity of the thiol compounds, caused by an increase of either concentration, pH or temperature, can be explained by an increase of the amount of thiol compound present inside the cell. The differences in radio-protective activity of the various compounds cannot be explained by differences in cellular uptake. The thiol compounds with a pK-value lower than 10 appeared to be very toxic at concentrations between 0.1 and 2.0 m[image], but not at concentrations lower than 0.1 m[image] and between 2 to c."T00 m[image]. This striking toxicity could be prevented by incubation under anoxic conditions, by a decrease of the pH to 6.3, by addition of an excess of another thiol compound or of KCN, but not by addition of Na2S2O3. The toxic action of the thiol compounds at these concentrations seems to be caused by an irreversible intracellular reaction of a specific oxidation product of these compounds with some cellular constituant.