NEW EVIDENCE ON THE MECHANISM OF 

 EADIATION LEUKAEMOGENESISt 



I. BERENBLUM and N. TRAININ 



The Weizmann Institute of Science, Rehovoth, Israel 



The work to be presented here arose from an attempt to apply some of the 

 principles of experimental carcinogenesis to radiation leukaemogenesis. Such 

 an approach has the advantage of making use of the accumulated evidence, 

 the special techniques, and some of the theorizing, from the broad field of 

 carcinogenesis. There is, however, a possible danger to be guarded against, 

 which hardly needs stressing before this audience — of looking upon radiation 

 merely as another carcinogenic tool among the hundreds already known, and 

 of underestimating the importance of the unique properties of ionizing 

 radiation in relation to the over-aU biological response. 



A few introductory remarks about the mechanism of carcinogenesis in 

 general, before turning to the specific problem of radiation leukaemogenesis, 

 should make the relationship clearer. 



One of the crucial problems of carcinogenesis is the existence of a very long 

 latent period, during which no morphological evidence of neoplasia is detect- 

 able. Even when one extrapolates the growth-curve of a tumour to its morpho- 

 logical zero point, when, presumably, the neoj)lastic change is still confined to 

 a single ceU, there is stUl a very long latent period preceding it, which must 

 be accounted for in the carcmogenic process. The state of "pre-neoplasia" is, 

 thus, more a functional than a morphological problem. 



We now know that, in the case of skin at least, the changes during the long 

 latent period do not constitute a single continuous process, but are made up 

 of separate components — a sort of "biological chain reaction", by analogy 

 with the familiar "biochemical chain reactions" in cellular metabolism. 



In skin carcinogenesis, two consecutive processes — -"initiation" and 

 "promotion" — are now clearly defined, each of which can be separately 

 induced by artificial means. One of the most effective initiating agents for 

 mouse skin is urethane, or ethyl carbamate (Salaman and Roe, 1953); the 

 most potent promoting agent for mouse skin is croton oil (Berenblum, 1941). 



Urethane alone is not carcinogenic for mouse skin; croton oil alone is to 

 some extent carcinogenic if the treatment is very prolonged. That their 



f A review based on work supported in part by a grant from the Joseph and Helen 

 Yeamans Levy Foundation and by research grant C-5455 of the National Cancer Institute, 

 U.S. Public Health Service. 



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