RADio-PRon-cnx 1. AcniON OF c:ertai\ amines 



available oxv<;cn should reduce the protective action. Koui main ways in 

 which this ijiobleni may be studied experimentally arc: 



(/) Alterations in calcuhited dill'usion gradients oi' ox)gen in relation to 

 cell sizes, and cell aggregates. 



(//■) Artificial inhibition of oxidative metabolism by substances such as 

 cyanide, which inactivate cytochrome, catalasc, etc.; or diniti (.phenol used 

 to uncouple phosphorylation from respiratoiy processes. 



(//■/) Alteration of cellular oxygen consumption by changes in environmental 

 temperature. 



(iv) Direct alterations in partial pressures of oxygen to which cells are 



exposed. 



Crabtree and Cramer^^ originally demonstrated that a reduction of 

 oxidative metabolism in tumour tissue in vitro, by chilling, or cyanide and 

 other enzyme poisons, increased radio-sensitivity in the presence of oxygen. 

 The differences in 'oxygen effect' observed between small and large cells, 

 single cell suspensions and cell aggregates are largely explained in relation to 

 diffusion gradients of oxygen from the medium to the interior of the cell. In 

 whole animals, most available evidence of the effect of increased available 

 oxygen within the cell, on the action of protective agents, relates to the effect 

 of cyanide. 



We have investigated and compared the effects of pretreatment with 

 cyanide, and pressurization of animals with pure oxygen during irradiation, 

 on the effects of certain protective agents in vivo in mice and rats. Only 

 preliminary results are available, conducted over the past five months, since 

 an experimental apparatus was designed and constructed. This apparatus 

 allows for the administration of pure gases or predetermined mixtures of 

 gases to animals at pressures of up to 120 lb. per sq. in. The rate of com- 

 pression and decompression of animals can be controlled and preset at 

 desired levels. Preliminary flushing of the chamber atmosphere gives levels 

 of purity of more than 95 per cent. Partial pressures of respired oxygen varying 

 from -05 to 5 • atmospheres have been used and the effects on the protective 

 action of cysteamine, cystamine, 5-hydroxytryptamine (5-OHT), histamine 

 and adrenalin, studied in both rats and mice. Preliminary studies and lethality 

 findings, are described in this paper. 



Action of Cyanide on Radiochemical Protection 

 Sodium cyanide itself was reported to give protection against irradiation in 

 C57 Black strain mice^-, but not in ratsi^. Mottram^'' reported that cyanide 

 enhanced radio-sensitivity of Viciafaha roots; Crabtree and Cramer^i found 

 similar enhancement of radiation effects for tumour cells, whilst HalP^ found 

 that cyanide did not alter tumour radio-sensitivity in vitro in the absence of 

 oxygen. Cyanide does not influence the sensitivity of bacteria — a finding 

 attributed to the free availability of intraceUular oxygen by diffusion from 

 the medium. 



In view of the contradictory findings in rats and mice, we have repeated 

 experiments using Swiss mice and both Wistar and Canberra black stock rats. 

 The results show that a dose of 0- 1 mg of NaCN in 25-g mice gives weak 

 protection against 1000 r whole-body irradiation. However, this protective 



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