MECHANISMS OF CHEMICAL RADIATION PROTECTION 303 



longer capable of repair. The ])rotective agent and oxygen are 

 therefore working in opposition and in this way the fact that pro- 

 tection in vivo is more marked in aei'ohic than in anaerobic 

 systems would be explained. 



By combining temporarily ivifh the fanjef m.olccAde and thereby 

 rendering it more radio-resistant. This effect was first demonstrated 

 by Dale (1942) who found that separately the prosthetic group 

 and the protein part of an enzyme were more readily inactivated 

 in dilute solution than the complete enzyme. Doherty (1952) 

 found that chymotrypsin was less radiosensitive when combined 

 with its substrate and several other examples of this type of pro- 

 tection have since been observed. Eldjarn and Pihl (1956) have 

 suggested that the sulphydryl-containing substances protect by 

 reacting by an exchange process with the — S.S — groups, the 

 destruction of which is assumed to constitute the primary lesion. 



PROTECTION BY CYSTEAMINE IN MODEL SYSTEMS 



In experiments with model substances cysteamine, which has been 

 found very effective for protecting animals (Bacq et al., 1951, 1953), 

 has been shown to be capable of functioning by all of the mechanisms 

 that have been discussed. 



(a) Competition for free radicals 



This has been demonstrated in several systems. Figure 1 shows its 

 action in preventing radiation damage of bovine serum albumin in 

 dilute solution. The amount of protein changed was determined from 

 the sedimentation diagram measured in the ultracentrifuge (Rosen et 

 al., 1957). The rate of reaction of cysteamine with free radicals is much 

 greater than that of the protein and almost all the cysteamine has to be 

 destroyed before there is an effect on the protein (i.e. the dose-response 

 curve has a threshold). However, even when the dose needed to change 

 all the cysteamine has been exceeded, the rate of destruction of protein 

 is still less than that in the unprotected solution. This is because the 

 radiolysis product of cysteamine is still a weak protector. This is not 

 the case with thiourea. 



It is quite clear here that protection does not occur by a disulphide 

 exchange process as postulated by Eldjarn and Pihl (1956) since in 

 native albumin none of the seventeen disulphide bonds can be reduced 

 by cysteamine because of steric inaccessibility. (Alexander and Hamil- 

 ton, 1960). 



