44 



I. BERENBLUM AND N. TRAININ 



strict sense of the term, but indirectly, by further depressing the activity of 

 the bone-marrow (cf. Kaplan and Brown, 1951). 



To test this alternative possibility, the effect of intravenous injections of 

 isologous normal bone-marrow suspension was investigated in relation to the 

 "two-stage" experimental system. It was found (Berenblum et at., 1961) that 

 while such treatment interfered with the over-all leukaemogenic action of 



Table II. LeuJcaemia induction in C57BL/6 mice resulting frorn single doses of 

 radiation followed or preceded by urethane 



total-body radiation, as had been previously demonstrated (Kaplan et ah, 

 1953), it did not interfere with the "promoting" phase brought about by 

 urethane (see Table III). 



We were thus led to conclude, despite our own earlier scepticism, that the 

 phenomenon observed did, in fact, represent a two-stage mechanism of 

 leukaemogenesis, in which low doses of radiation acted as initiating factor 

 and urethane as promoting factor. The significance of this conclusion was 

 two-fold, (i) It provided a broader basis for the fundamental study of the 

 mechanism of carcinogenesis in general, and (ii) it offered a more refined tool 

 for the study of leukaemogenesis. The latter is, naturally, the one that concerns 

 us most here, in this Symposium. 



Experiments were then set up, using the radiation-urethane two-stage 

 system as an analytical tool, to explore some of the complicating factors known 

 to be implicated in radiation leukaemogenesis, e.g. (a) the inhibition resulting 

 from shielding a part of the body (Kaplan and Brown, 1951), and the role of 

 bone-marrow in radiation leukaemogenesis (Kaplan et al., 1953); (h) the 

 prevention of leukaemogenesis by thymectomy, and its reversal by subsequent 

 implantation of unirradiated normal thymus (Kaplan et al., 1956); and (c) the 

 involvement of a specific leukaemia virus in radiation leukaemogenesis 

 (Gross, 1959; Lieberman and Kaplan, 1959). 



