LABORATORY STUDIES AND CLINICAL TRIALS OF CHEMICAL RADIO-SENSITIZERS 



cells in prophase and metaphase especially in lower concentrations. Similar 

 changes are found with the Ehrlich ascites tumour. 



Tissue-culture studies 



With regard to the general technique with tissue-culture experiments, 

 experimental developments during the past few years to study mitotic 

 inhibition, cytological effects generally and radio-sensitization by chemical 

 agents have proved satisfactory. Compound I and Compound XXVIII are 

 the usual reference substances. Probit analysis has been used. The study of 

 the combination of the action of X-radiation and Compound I by the sum- 

 mation method has demonstrated potentiation of both mitotic inhibition and 

 chromosome fragmentation (similar results have been obtained in some experi- 

 ments on the roots of Allium Cepa by Mr. K. C. Bora ; it has also been found 

 that in this material the compound 2-ethylenimino-l : 4-naphthoquinone pro- 

 duces gross inhibition of the growth of roots in concentration 10~^M). 



The problem of the thermal instability of Compound I which appeared to 

 account for some erratic results in some animal experiments and clinical trials, 

 appears to have been solved by the finding that this thermal instability is 

 associated with the presence of an easily removable impurity in the aqueous 

 solutions in the ampoules in the absence of oxygen (Dr. A. L. Morrison). 

 With the purified preparations of Compound I, it now seems possible to 

 obtain consistent results without the necessity to store the ampoules at 3° C. 



An interesting experiment by Mrs. Simon-Reuss is reaching completion 

 and will be reported in detail elsewhere. The influence of Synkavit and its 

 effects as a radio-sensitizer on chick fibroblasts in culture have been followed 

 after subcultivation for up to 17 passages. A pure strain of chick fibroblasts 

 was divided into batches of cultures ; one batch was treated with Synkavit 

 for 24 hours in concentrations 2, 3, 4 x 10~^M respectively in different 

 experiments. The other cultures were kept for controls for testing the effects 

 of Synkavit and of irradiation. The whole strain was subcultured every 

 48 hours, washed in Tyrode solution and transferred to fresh medium con- 

 sisting of plasma and embryo extract only. At various intervals six cultures 

 were taken from each group and the group formerly treated with Synkavit 

 was irradiated at 18 hours and a control group was similarly irradiated. 

 Further, one of the treated groups and one of the untreated groups were kept 

 as controls. These cultures were fixed and stained and counted after 

 24 hours. The experiments lasted for 16, 16 and 17 passages, respectively 

 for 5-54- weeks. The cultures originally treated with Synkavit alone showed 

 no abnormality and no mitotic inhibition and were in no way diflferent in 

 appearance from the controls. The untreated cultures irradiated with 150r 

 showed 22-28 per cent mitotic inhibition throughout the whole experiment. 

 Those treated originally with 2 X 10~^M Synkavit and irradiated with 150r 

 showed mitotic inhibition starting off' with 75 per cent for three passages, 

 then falling to 60 per cent at the sixth passage and 26 per cent at the tenth 

 passage. The cultures originally treated with 4 X 10~^M Synkavit showed 

 no inhibition and no cytological abnormality. 300 r produced 40 per cent 

 inhibition in the controls, but 300 r administered to the subcultures of the 

 strain originally treated with Synkavit showed 94 per cent mitotic inhibition 

 persisting for several subcultures with 80 per cent at the fourteenth passage 



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