LEUKAEMIA INDUCED in RAl )IA 1 ION 



own cells which were damaged by radiation. Ford^^ has been able to 

 identify a number of clones of cells with characteristic chromosomal lesions 

 but we have yet to sec such a clone exhibiting signs of malignancy. Chromo- 

 somal lesions by themselves do not srcm to account for the malignant 

 change. 



One ought, therefore, to consider the other postulate — evolution by small 

 steps from an original iioinial cell. Kaplan et al.^^ may have produced 

 examples of this. From their previous work they have found that thymectomy 

 abolishes the liability of C57BL mice, irradiated with set courses of X-rays, 

 to develop thymic leukaemia. They found that reimplantation of a normal 

 thymus into such thymectomized irradiated animals restored to a certain 

 extent the tendency to develop leukaemia, and, what was more remarkable, 

 that the leukaemia frequently arose from the cells of the normal implant. 

 This observation has been confirmed with other stocks by Law and Potter ^^ 

 and ourselves^". To explain this plienomenon Kaplan ^^ is now considering 

 how radiation could act through indirect mechanisms. He postulates that the 

 disturbance of the internal environment may favour the selection of chance 

 mutants, or may encourage abnormal repair. In the latter case step by 

 step changes could be envisaged particularly if growth were cyclical. A 

 further suggestion by Kaplan was that the radiation might activate a 

 pro virus. 



Certainly as far as murine leukaemia is concerned a viral aetiology is 

 now a fashionable concept. Gross ^^ has for years been arguing the case and 

 reporting his experimental evidence for it. In his hands a cell-free extract 

 from leukaemic tissue of AK mice has been able to induce lymphoid leuk- 

 aemia in the Bittner sub-line of C3H mice which normally develop leukaemia 

 most rarely. In the early stages of this work Gross found it necessary to 

 inject the cell-free extract into the mice when newborn. Our interpretation^' 

 was that it was necessary for him to induce immunological tolerance of the 

 host for the 'agent'. More recently Gross has been able, by serial passage of 

 agent through a number of newborn hosts, to produce a still more potent 

 extract which will induce leukaemia even in his adult C3H mice. If this is 

 confirmed, my first reaction would be that a hypothesis involving immuno- 

 logical paralysis would explain the effect. However, after injection of both 

 the newborn with weakly active and the adult with strongly active material 

 there is an appreciable interval of months before the leukaemia is manifest. 

 A similar latent period is seen between application of 'inducing' agents such 

 as X-rays, carcinogenic chemicals, etc., and the manifestation, but in this 

 case no particularly receptive host (such as the C3HBi) need be chosen: 

 mice of all strains will develop leukaemia if suitably irradiated. And, indeed. 

 Gross now has obtained active extracts from irradiated mice, though we^', 

 certainly less experienced in this field of 'extraction', have not been suc- 

 cessful. If, therefore, the virus theory is to be extended by Gross to account 

 for most if not all mouse leukaemia, the virus must be universally present in 

 mouse stocks. It does not seem to me necessary to invoke an 'activation' 

 and to compare the process with activation of lysogenic bacteria, as Gross 

 has certainly done and I presume Kaplan to have done also. The con- 

 ditions under which Gross induces his leukaemias and other tumours are 

 similar to those whereby Stewart and Eddy-" have recently produced 



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