RADIATION INJURY AND LETHALITY 443 



Such "secondary" effects are not unusual in toxicology, of course, and 

 their period of latency may depend on the length of time the organism 

 can get along without some essential function. Cyanide kills very rap- 

 idly because it inhibits oxidative processes which are immediately neces- 

 sary for life; removal of the kidneys, or some poison which has the same 

 physiological effect, has a latency of lethal effect while metabolic prod- 

 ucts are accumulating to a lethal point. Interference with enzyme func- 

 tion, if irreversible, may allow similar accumulation of undesirable mat- 

 ter or prevent the formation of a necessary substrate; the toxic level of 

 the first or the reserve supply of the second will determine the latency. 



Previous panels of this symposium have dealt with radiation biochem- 

 istry and cytology. It is therefore proper now to consider the question 

 of latency in cytological terms. Here it is much easier to contrive a fit 

 between the known loss of specific tissue elements and the clinical syn- 

 drome of acute and subacute radiation sickness^between, perhaps, ter- 

 tiary and quaternary radiation effects. The damage to the red-cell- 

 forming tissues has obvious end results; that to the granulopoietic func- 

 tion reduces the threshold of resistance to infectious invasion; the result 

 is invasion by organisms which may have been latent in tissues or may 

 have gained entrance through cytological discontinuities in the digestive 

 tract or elsewhere (9, 10). It has long been known that many of the 

 features of the acute radiation syndrome resemble responses to infection, 

 including fever and associated signs, death in a shock-like state, and even 

 the improved kidney function in the middle stages (11). It may be 

 significant that the responses of certain species having different suscepti- 

 biHties correlate well with degrees of damage to the granulopoietic sys- 

 tem (12, 13). 



The bleeding tendency is related in part to a disappearance of blood 

 platelets (again on a cytological basis) and in part to the appearance in 

 blood of substances which, like heparin, interfere with coagulation, and 

 it is not certain that these tw^o parts make up the whole (14). The re- 

 lation of the lymphocyte to the immune processes brings in another cyto- 

 logical mediation which deserves further study, since the immune func- 

 tions are interfered with in irradiation (15-17). 



It is frequently suggested that a part of the toxic picture is due to 

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

 organism is unable to handle in a normal fashion. This is, for several 

 reasons, one of the most difficult problems to solve in the physiological 

 laboratory. For the sake of completeness, we may mention that ste- 

 rility and falling of hair would appear to have a cytological basis. 



Whether the cell destruction we have been observing occurs through 

 a mechanism of chromosome damage remains an open question. We 



