IM l.UENCE OF OXYGKN ON RADIO-SENSITI\ I IT OF CELLS AND TISSUES 



It will be seen that the species O^ can be formed by electron attachment 

 to O, as well as by the formation and dissociation of HOo • . This species 

 has been postulated •*! as an intermediate in the inactivation of 'dry' trypsin, 

 the yield of which is somewhat increased In' oxygen under X irradiation but 

 not under a radiation. 



The readiness with which oxygen combines with other radicals is attri- 

 butable to its own bi-radical character, i.e. to the fact that it has two unpaired 

 electrons. These unpaired electrons also confer the property of paramag- 

 netism. While almost all the common gases arc diamagnetic, there are three 

 which share \vith oxygen the property of being paramagnetic by virtue 

 of possessing an unpaired valance electron. These are, nitric oxide, nitrogen 

 dioxide and chlorine dioxide, and it occurred to Howard-Flanders to see 

 whether nitric oxide could play the role of oxygen in the initiation of radio- 

 biological damage. As reported recently"', he was rewarded by finding that 

 when Shii^ellafcxricri are rendered completely anoxic and exposed to X-rays 

 after equilibration with a mixture of nitric oxide and nitrogen containing 

 less than 1 per cent nitric oxide, the bacteria are as sensitive as when fully 

 aerobic. Kihlman has recently reported "^ that nitric oxide similarly raises 

 the sensitivity of anoxic roots {Vicia faba) , and we have found that the sensi- 

 tivity of anaerobic Ehrlich ascites tumour cells is raised approximately to the 

 aerobic level by equilibration with nitric oxide/nitrogen mixtures"''. Howard- 

 Flanders'* has estimated that molecule for molecule nitric oxide and 

 oxygen have about the same influence on radio-sensitivity, and Kihlman"^ 

 (personal communication) has reached a similar conclusion from his studies 

 of chromosome damage in Vicia meristem cells. Although not a metabolite 

 in the ordinary sense, nitric oxide is believed to be an intermediate in the 

 metabolism of certain micro-organisms and it can combine reversibly with 

 haemoglobin"^ and reduced cytochrome oxidase. Biochemical as well as 

 radio-chemical mechanisms, therefore, might be invoked to account for the 

 observed phenomenon. If this were the case the relation between radio- 

 sensitivity and nitric oxide concentration would presumably reflect the 

 proportion of some pigment molecules with which the nitric oxide is com- 

 bined at a given nitric oxide concentration, but the apparent identity of the 

 sensitivity-concentration relation for nitric oxide and oxygen would then 

 be very remarkable since it would imply equal affinity of the pigment for 

 these two molecules. The fact that temperature has little or no influence on 

 the form of the sensitivity-concentration relation in the case of oxygen* 

 is also against the view that this relation reflects the reversible dissociation 

 of an organic complex with oxygen. 



Nitric oxide is well known to chemists as a powerful scavenger of free 

 radicals, but the reaction rates of nitric oxide with photo-initiated free radi- 

 cals are known in some instances to be very difl'erent from those of oxygen 

 (R. H. Fallen— personal communication). Moreover, nitric oxide having 

 only one unpaired electron should react with only one free radical to form 

 a stable product, whereas the combination of oxygen, which has two un- 

 paired electrons, with a free radical yields a product which is still a free 

 radical. The addition of oxygen to organic free radicals frequently leads to 



* Current investigations by the author and colleagues with Ehrlich ascites tumour cells 

 and with bacteria. The contrary statement by Howard-Flanders-^ has been withdrawn. 



166 



