042 RADIATION BIOLOGY 



entities also have the capacity to dimmish many of the effects of X rays 

 in mammals. Cysteine (Patt, Tyree, et ah, 1949; Patt, Smith, et ah, 

 1950; Smith, Patt, Tyree, and Straube, 1950; Patt, Smith, and Jackson, 

 1950), glutathione (Patt, Smith, Tyree, and Straube, 1950; Chapman 

 and Cronkite, 1950; Chapman et ah, 1950), and BAL (Smith, Patt, and 

 Tyree, 1950) have been shown to reduce acute toxicity in mice, rats, and 

 dogs. Some degree of protection has been seen also with thiourea 

 (Limperos and Mosher, 1950; Mole et ah, 1950), dithiophosphonate 

 (Mole et ah, 1950), and massive amounts of glucose (Loiseleur and Velley, 

 1950a; Baclesse and Loiseleur, 1947) and ethanol (Paterson and 

 Matthews, 1951; Patt, Mayer, and Smith, 1951a). The action of these 

 protective substances against repeated low-dose irradiation has not, to 

 our knowledge, been evaluated. Protection against the chronic sequelae 

 of irradiation is also largely undetermined. 



It is perhaps significant that cystine, methionine, and ascorbic acid do 

 not modify sensitivity in the mammal (Patt, Smith, Tyree, and Straube, 

 1950). While all reducing agents do not appear to protect against the 

 acute lethal action of ionizing radiations, e.g., ascorbic acid, hydrosulfite, 

 tetraborohydride, mercaptosuccinate, and thiosulfate, this may be a 

 consequence of their temporal and spatial distribution and biological life 

 (Patt, Blackford, et ah, 1951; Patt, Mayer, and Smith, 1951a). 



The time course of the protection against the acute effects of radiation 

 may follow a somewhat different pattern in the intact animal and in 

 certain in vitro systems. In general, however, these substances must be 

 given before irradiation to be effective. Thus, the optimal time of 

 cysteine administration in rats and mice is immediately before exposure, 

 and there is no postirradiation effect (Patt, Smith, Tyree, and Straube, 

 1950). Although some improvement of survival has been observed in a 

 small series of rabbits after treatment with cysteine plus ascorbic acid 

 during the first two postexposure hours (Loiseleur and Velley, 1950b), 

 this has not been verified in either rabbits or mice (Patt, Mayer, and 

 Smith, 1951b). On the other hand, the survival of thymocytes irradi- 

 ated in vitro is increased to the same degree whether cysteine is added 

 one minute before or after the exposure (Patt, Blackford, and Straube, 

 1952). Cysteine addition 15 to 30 minutes before X irradiation is 

 optimal, however. There is no satisfactory explanation for the apparent 

 discrepancy other than to implicate possible differences in the kinetics of 

 the reactions with cysteine and in the time constants for the develop- 

 ment of irreversible injury in the thymic cell suspension and in the intact 

 animal. 



It has been suggested that glutathione protects animals by promoting 

 regenerative mechanisms and not by preventing cellular destruction 

 (Cronkite et ah, 1951). The basis for this interesting concept rests in 

 the similarity of changes in organ weights, peripheral blood counts, and 



