HARVEY M. PATT 



is added to a thymus lymphocyte suspension immediately after X-irradia- 

 tion^^. This can be attributed only in part to the persistence of toxic 

 substances in the medium. Differences in the time course of protection of 

 various systems may be related perhaps to differences in the kinetics of 

 reactions with cysteine and in the time constants for development of irre- 

 versible injury. Thymus cells suspended in the test tube represent a fairly 

 sluggish system in which oxygen is rate limiting for the disappearance of 

 cysteine. On the other hand, the systems most responsible for acute 

 lethality of the living animal are those with a rapid turnover in which the 

 chances for intersection of a chain of events are limited accordingly. The 

 possibility exists that some in vivo responses may be amenable to prompt 

 post-irradiation modification by chemicals of this type. 



Of considerable interest is the fact that cysteine protection in mice is an 

 inverse function of ionization density, being less for fast neutrons than for 

 gamma rays or X-rays^*'. This finding parallels the oxygen effect in irradi- 

 ated systems and is supported by other data^^ It may be stated that 

 cysteine does not protect thymus lymphocytes in the absence of oxygen i^. 

 The resistance of packed thymocytes and the failure of cysteine to protect 

 them may be attributed to their hypoxic state. Cells equilibrated with 

 oxygen before packing by centrifugation appear to be as sensitive as cells in 

 suspension and are readily protected. This is interpreted as evidence for a 

 cellular site of action which is implicated also from studies with tumour 

 fragments. It should be noted that there is a rapid uptake of oxygen and 

 an increase in lactic acid when cysteine is added to the thymic cell suspen- 

 sion. These data suggest perhaps that its action is related to, although not 

 necessarily the direct consequence of, the availability of intracellular oxygen. 

 Potentiation of the protection of the intact animal by suitable dosages of 

 dinitrophenol or sodium nitrite or by 10 per cent oxygen^^ its inhibition 

 by high oxygen tensions i^, and the finding of an increase in the arteriovenous 

 oxygen difference after cysteine injection i'* may also be thought of as sup- 

 portive evidence for this interpretation. It should be remarked that the 

 oxygen content of mixed venous blood does not necessarily reflect the situa- 

 tion in various loci ; hence the failure to detect a change with [i-mercapto- 

 ethylamine^o does not exclude a possible role of oxygen in the protective 

 mechanism. It may be noted also that the dosages used were considerably 

 below those required for protective effects in other species. 



Certain parallels have been drawn between oxygen poisoning and X- 

 irradiation and may signify a common primary mechanism of action through 

 oxidizing free radical formation as suggested by Gerschman et aP^. It may 

 be noted in particular that some substances that are protective against 

 X-ray injury are also effective against oxygen poisoning. It is well to recall 

 that the time course of the two syndromes differs widely unless many thous- 

 ands of roentgens are used. This may reflect differences in concentration 

 and distribution of the toxic intermediates produced in the two situations, 

 although other interpretations are possible and perhaps more likely. 



It appears that mechanisms other than the immediate oxidative reactions 

 induced by activated water may also be involved in this form of protection 

 against X-radiation. It has been observed, for example, that protection of 

 thymocytes in suspension by cysteine is dependent upon temperature during 



107 



