PHYSICAL AND BIOLOGICAL FACTORS 943 



histologic appearance of certain radiosensitive tissues in treated and 

 untreated mice during the first few days after exposure to a nearly com- 

 pletely lethal dose. These findings do not, however, constitute incon- 

 trovertible proof of failure to prevent injury. There is reason to believe 

 that histologic changes, in general, reflect the amount of radiation and 

 not the lethal effect on the animal and, moreover, that the threshold point 

 of maximal change may be below that required for acute lethality (Bloom, 

 1947; De Bruyn, 1948). These considerations can also explain the failure 

 to observe a protective effect of glutathione on organ weights (Cronkite 

 et at., 1951) and of glutathione and cysteine on the uptake of iron in the 

 red blood cells of irradiated animals (Hennessy and Huff, 1950; Hennessy 

 and Folsom, 1950; Hennessy, Folsom, and Glover, 1950). For example, 

 the anticipated difference in the organ weights between 600 and 800 r, 

 which represents the degree of protection by glutathione on the basis of 

 survival data (Chapman, Sipe, et al., 1950), is only about 5 per cent 

 (Carter et al., 1950). The failure to detect a difference in the heterophil 

 and erythrocyte levels in the peripheral blood of glutathione-treated and 

 untreated mice is not readily explained, however (Cronkite et al., 1951). 



As contrasted with the view that protection in the mammal results 

 from some facilitation of recovery rather than prevention of injury, there 

 is a body of evidence indicating that sulfhydryl compounds can diminish 

 cellular destruction incident to X-ray exposure. Cysteine has been 

 shown to decrease damage to the skin (Forssberg, 1950) and lens (von 

 Sallmann et al., 1951) after local irradiation and to increase the resistance 

 of tumor cells (Straube et al., 1950; Hall, 1951). Thymic cells have also 

 been protected in vitro over a dosage range of 50 to 2000 r (Patt, Black- 

 ford, and Straube, 1952). Furthermore, there are indications that 

 cysteine can modify significantly the hematologic changes in irradiated 

 rats (Patt, Smith, and Jackson, 1950; Rosenthal et al, 1950). Indeed, 

 the changes that have been observed in rats irradiated with 800 r after 

 cysteine treatment compare favorably with those observed after a sub- 

 lethal exposure of 300 r (Patt, Smith, and Jackson, 1950). These con- 

 siderations suggest that cysteine may raise the threshold for radiation 

 effects in general, with the probable exception of those attributable to 

 direct ionization. 



The mechanism of chemical protection is poorly understood. Protec- 

 tive substances may increase the resistance to X rays by modifying 

 activated water reactions, the nature of the biological targets, or the 

 redox equilibrium of the cell. It is of interest that a given amount of 

 cysteine accounts for a rather constant percentage of the biological 

 effect of the radiation over a wide dose range (Patt, Blackford, and 

 Straube, 1952; Patt, Mayer, Straube, and Jackson, in press). This has 

 been observed in survival studies with thymic cells and with mice, but, 

 unfortunately, can be explained equally well by postulating an interaction 



