L. H. GRAY 



By its presence within the cell oxygen may control regional Redox 

 potentials, and in particular the Redox condition of the respiratory enzymes; 

 it may, through the pathway of oxidative phosphorylation, provide an essen- 

 tial source of energy for the development of initial physical and chemical 

 disturbances into manifest biological lesions ; it may, by virtue of its own bi- 

 radical character react with radiation induced radicals so as to convert 

 reversible or innocuous chemical changes into forms incompatible with normal 

 cellular activity; or again, operating at the chemical level, the oxygen mole- 

 cule may, by virtue of its paramagnetic properties, alter the probability of 

 transition in either direction between singlet and triplet states, or through its 

 electron affinity alter the steps involved in charge neutralization following 

 the ionization of the medium by charged particles. 



We may refer briefly to a few of the experiments which have been stimu- 

 lated by one or other of these considerations. It was natural that an answer 

 should first have been sought biochemically in terms of a greater suscepti- 

 bihty of the aerobically metabolizing cell. This was the approach of Crab- 

 treei", whose results are summarized in Table 4. All these results were care- 

 fully checked with three different transplantable mouse tumours. The 



Table 4. Radio-sensitivitv 



Increased Decreased Unaltered 



HCN treatment Na-anaerobiosis at 37-5°C ICH,.COONa treatment 



Aerobiosis at 0"C CO-anaerobiosis at 37-5°C NaF treatment 



Nj-anaerobiosis at 0°C Variations in glucose concentration 



Variations in pH 



cyanide and iodoacetate were used at concentrations which greatly depressed 

 respiration and glycolysis respectively in these particular tumours, without 

 influencing the proportion of takes on re-inoculation. If it is correct to inter- 

 pret the effect of cyanide and low temperature as due to the reduction or 

 abolition of oxygen gradients through the tumour fragments, then Table 4 

 shows no effect of any of the enzyme poisons tested in these particular cells. 

 All Crabtree's observations are compatible with the view that radio- 

 sensitivity is controlled by availability of oxygen to the tumour cells — i.e. 

 by the presence or absence of dissolved molecular oxygen. Subsequent work, 

 however, has revealed a number of cases in which enzyme poisons can 

 influence sensitivity in the presence of dissolved oxygen {Table 5). 

 No very consistent pattern is discernible, A 2-5-hour pre-treatment with 

 carbon monoxide abolishes oxygen sensitivity in grasshopper embryos — in 

 the dark but not in the light, suggesting a cytochrome mechanism — but a 

 half-hour pre-treatment with carbon monoxide under pressure enhances 

 the oxygen-dependent sensitivity of microspores and roots. Cyanide treat- 

 ment during irradiation (with abundant oxygen present) has no effect on 

 tumours, grasshopper embryos, and roots, but suppresses the oxygen- 

 dependent sensitivity in Sarcina lutea. 



In order to throw light on the possible role of the cytochrome system, 

 Moustacchi-3 has compared the aerobic and anaerobic sensitivities of three 



161 



