200 CELLULAR METABOLISM 



Irradiation leads to enzyme inactivation, followed by partial or total 

 blockage of some normal, and a simultaneous opening of other, possibly 

 noxious, pathways. Cyanide inactivates enzymes, but interferes pri- 

 marily with other processes, as do the decomposition products of water, 

 which are responsible for much of the irradiation effect. It is possible 

 that cyanide, by blocking the noxious pathw^ays, makes the x-ray effect 

 less lethal. If the x-ray does not exceed 700 r the noxious pathway is 

 intercepted. The primary x-ray lesion has now sufficient time to be 

 healed. A somewhat different explanation of the protecting effect of 

 cyanide is discussed on p. 202. 



Irradiation with a lethal dose is followed among other processes by 

 formation of fatty liver in the mouse as a result of interference with 

 the normal path of carbohydrate and/or fat metabolism. The liver of 

 cyanide-injected irradiated animals shows a much less pronounced fat 

 deposition (43). It is also of interest to remark that acute death in the 

 chick is associated with rapid accumulation of uric acid in blood and 

 tissues (44). We have here an example of a toxic picture due to the 

 insult of materials discharged from injured cells at a rate which the 

 organism is unable to handle in a normal fashion. 



The period of 50 per cent survival in mice given 350 r of x-rays was 

 doubled by 22 daily injections of 15 Mg of folic acid, beginning 7 days 

 before irradiation. Pyridoxine had a similar effect (45). 



A protective effect produced by numerous other substances, as, for 

 example, desoxycorticosterone (46) or atropin, was reported as well (47). 

 Even changes in the diet have been reported to influence the mortality 

 rate of the guinea pig due to irradiation with 100-600 r (48). 



Ionizing radiation produces a contracture of the stimulated frog mus- 

 cle. Bacq (49) attributed this effect to the inactivation of the enzyme 

 systems involved in carbohydrate metabolism in muscle. Another ex- 

 planation has been advanced by Barron (50), who feels that oxidation 

 Qf the — SH groups of myosin is responsible for the observed inactivation. 

 Irradiation and small amounts of mustard and of some other com- 

 pounds (3, 110) all influence the mitotic cycle in a similar way and are, 

 among other factors, very effective in activation of the phosphate- 

 transferring — SH enzyme phosphokinase. Therefore, the possible effect 

 of the inactivation of this enzyme on desoxyribonucleic acid synthesis, 

 among others, has to be considered (51). 



Also included in the enzymes to be considered is adenosinetriphospha- 

 tase, which can be inactivated in vitro by irradiation with very modest 

 doses (31), though only in the absence of protecting substances. 



Inactivation of this enzyme may interfere with carbohydrate metabo- 

 lism, but it is also conceivable that adenosinetriphosphatase is involved 



