THE PHYSIOLOGICAL RESPONSE TO RADIATION AND TO RADIOMIMETIC CHEMICALS 



action of the radiation on the tissues. In this connection it would be inter- 

 esting to know the effect of radiation protective agents such as cysteamine 

 on the different phases of the radiation response as it is possible that such 

 agents may have more effect on one reaction than the other. One would 

 of course also want to know how these protective agents influence the response 

 to radiomimetic chemicals such as Myleran and CB 1348. 



With regard to the mechanism of action of the radiomimetic chemicals 

 both Myleran and CB 1348 show the same type of chemical reactivity 

 ' alkylation ' but whilst the nitrogen mustard CB 1 348 acts by means of an 

 Sni-type of reaction mechanism (Ross^^) Myleran acts mainly by the slower 

 Sng-type mechanism. Both compounds could therefore have cytotoxic 

 properties related to their common ability to alkylate, but the different type 

 of reaction mechanism of Myleran could result in more specific biological 

 properties, since, as pointed out by Ross^'^, the degree of reactivity of a sub- 

 stance by the Sug mechanism is controlled by the concentration of reacting 

 groups with which the chemical comes in contact. It seems possible that 

 a high concentration of active groups could occur during certain stages in 

 cell division, so that compounds of the Myleran type might tend to have 

 some degree of selective action on dividing rather than on ' resting ' cells. 



ACKNOWLEDGEMENTS 



This hivestigation has been supported by grants to the Chester Beatty Research Institute, 

 from the British Empire Cancer Campaign, the Jane Coffin Childs Memorial Fund for 

 Medical Research, the Anna Fuller Fund, and the National Cancer Institute of the 

 National Institution of Health, U.S. Public Health Service. 



REFERENCES 



^ Lamerton, L. F., Elson, L. A., and Christensen, W. R. Brit. J. Radiol. 1953, 26 



510. 

 2 Lamerton, L. F., Elson, L. A. and Harris, E. B. ibid, 1953, 26 568. 

 ^ Lamerton, L. F. and Baxter, C. F. ibid, 1954, in press. 

 " Haddow, a., Scott, C. M. and Scott, J. D. Proc. Roy. Soc. B, 1937, 122 477. 



5 Everett, J. L., Roberts, J. J. and Ross, W. C. J. J. Chem. Soc. 1953, 486 2386. 



6 Haddow, A. and Timmis, G. M. Lancet. 1953, 264 207. 

 ' Galton, D. a. G. ibid, 1953, 264 208. 



8 Elson, L. A. and Warren, F. L. Brit. J. Cancer. 1947, 1 86. 



^ Elson, L. A. Acta Un. internal. Cancer, 1948, 6 396. 

 ^° Elson, L. A. Brit. J. Haematol, 1954, in press. 



'^ Ross, W. C. J. Advances in Cancer Research, I 397. New York, N.Y., Academic 

 Press, 1953. 



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