J. F. LOUTIT 



of the leukaemia ; in some cases the leukaemia was given subcutaneously, in 

 others intravenously. In the later experiments we settled for the intravenous 

 route, because this \vas the severer test, resulting in a shorter time between 

 inoculation and death from leukaemia of untreated animals, (17 + 0-7 days 

 (I.V. series) and 28+1-9 days (S.C. series) for 151/1, between the sixth and 

 13th passages) ; also, in the treated animals, the clinical results were less good 

 when the leukaemic cells had been given intravenously. 



It was not possible to ensure that the leukaemias did not alter with the 

 passage of time. There was a strong clinical impression, supported by 

 observations on the time taken to kill control animals, that after periods of 

 relative stability the two leukaemias 151/1 and 151/2 became more 'malig- 

 nant'. We attribute our earlier therapeutic successes and later failures to 

 this cause. However, from our very limited experience with a mere handful 

 of transmissible leukaemias it does seem that not all leukaemias of recent 

 origin, and in their early generations of passage, are necessarily amenable 

 to this form of treatment. It is perhaps to be expected that in the mouse, 

 as in man, a leukaemia may be acute, sub-acute or chronic, reflecting the 

 intrinsic 'malignancy' of that individual line. Furthermore, mere age and 

 high numbers of generations of passage need not necessarily make for in- 

 creased 'malignancy'. In other studies of this type, Hewitt and Wilson^* 

 have, it is true, failed to treat successfully a CBA leukaemia of some con- 

 siderable age in terms of generations of passage, but Trentin^^ has had some 

 successes in treating the Gardner lymphosarcoma, which is a leukaemia of 

 considerable age. 



In the earlier stages of the work we kept the time of treatment constant — 

 seven days after inoculation. However, this does not ensure that the leukaemia 

 is at the same stage of dissemination if there is variation between generations 

 of passage of an individual leukaemia, or if there is variation between leuk- 

 aemias. Presumably, the greater the spread of the disease, and the greater 

 the number of leukaemic cells present, the more difficult it would be to effect 

 elimination of all the malignant cells. 



Variations of the total dose given, and of the dose rate, are possibilities, 

 and our experiences are extremely limited. The malignant cells may be 

 killed by the effects of the radiation interfering with the mechanisms of 

 mitosis, or by direct cytotoxic effect, as is characteristic in small lymphocytes. 

 Neither mechanism is more than vaguely understood, so that until these 

 fundamentals are worked out, particular schedules of irradiation are based 

 on empiricism. 



As a general conclusion we might say that the material presented above 

 does suggest that, under some conditions which cannot be defined, some 

 transmitted leukaemias are radio-curable. Preliminary studies by Simonsen 

 el al.^^ suggest that the same may be true of some leukaemias indigenous to 

 the treated animal, and induced by chemical carcinogens. The possibility 

 of using adjuvants, such as chemical cell-toxins or immunological reactions, 

 to supplement the effect of the irradiation might well be explored. 



REFERENCES 



^Jacobson, L. O., Simmons, E. L., Marks, E. K., Gaston, E. O., Robson, M. J. 

 and Eldredge, J. H. /. Lab. din. Med. 37 (1951) 683 



5 53 



