LABORATORY STUDIES AND CLINICAL TRIALS OF CHEMICAL RADIO-SENSITIZERS 



Sterile normal solution of saline and 4 received no injections whatsoever. In the 

 group of rats which received saline injections there were no deaths at 31 days after 

 irradiation. In the group of rats which received Synkavit injections there was only 

 1 survival at 31 days, the remainder dying within 12-16 days. The 4 control 

 (X-rays only) rats survived 31 days. 



MICROSCOPICAL 



The spleen and adrenals of both rats and rabbits were examined in these experiments. 

 The adrenal has been comparatively little studied, and yet is considered in the 

 recent literature to play some part in the syndrome of irradiation sickness (Porter*, 

 1952), and in the repair of tissue damage following irradiation (CRAVERf, 1948). 

 The importance of adrenal hormones in maintaining many vital functions also 

 suggest a potential connection between this organ and the widespread changes 

 present after irradiation. 



Spleen 



The changes in the spleen followed the same pattern in both species and were of the 

 type previously described in the mouse by Jacobson et al% (1950). The lymphoid 

 follicles disappeared rapidly in the first three weeks. In many of the animals dying 

 in the earlier period there were further changes of an atrophic nature, in some cases 

 little except blood vessels and fibrous tissue being seen. Iron containing pigment 

 was often prominent in those specimens. There was in general no difference 

 between animals given Synkavit and the controls dying after the same period. 



Rabbits 



In general the findings in these species are similar to those of Engelstad and Tor- 

 GERSEN§. The changes in the cytoplasm consist of loss of lipoid at an early stage 

 and in some cases a marked basophilia. This latter tends to disappear but lipoid 

 is slow to reappear in comparison with what is usually seen in secondary adrenal 

 involvement, often being small in amount at the end of 31 days. The nuclear 

 changes affect particularly the zona fasciculata extending up to the medulla (the 

 zona reticularis is hardly distinguishable in the rabbit). These come on after 3-5 

 days and appear to persist for weeks. The nuclei may undergo any of the commonly 

 seen forms of degeneration, pyknosis, fragmentation or loss of basophilia followed by 

 dissolution. Apart from occasional initial hyperaemia there is no inflammatory 

 reaction and one has the impression that some of the degenerated cells remain 

 in situ almost indefinitely. How much function may remain in spite of the nuclear 

 changes is an interesting point for further study. 



In contrast to the constant degenerative changes in the inner zones of the cortex, 

 the zona glomerulosa in the rabbit shows comparatively slight damage. Both 

 cytoplasm and nuclei appear relatively normal. No mitosis was seen in the rabbit 

 material, but in the presence of some of the relatively normal cells its occurrence 

 cannot be excluded on the present evidence. 



Rats 



In the irradiated animals it was found that, unlike what had been seen in the rabbit, 

 all zones seemed equally affected, showing cytoplasmic and nuclear changes. The 

 cytoplasmic damage was similar to that seen in the rabbit. The nuclear alterations 



* Porter, E. C. Radiol. 1952, 58 246-257. 

 t Graver, B. N. Amer. J. Roentgenol. 1948, 59 404-407. 



X Jacobson, L. O., Simmons, E. L., Marks, E. K., Robson, M. J., Bethard, W. F. and 

 Gaston, E. O. J. Lab. Clin. Med. 1950, 35 746-770. 



§ Engelstadt, R. B. and Torgersen, O. Acta Radiol. 1937, 18 671-687. 



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