J. F. LOUTIT 



or form (of one or more individual chromosomes), or l)oth. This is in marked 

 contrast to normal reticular tissue, the cells of which show little or no 

 variation of chromosome number and no change of chromosome form. 

 (ii) Usually the chromosomal variation in a leukaemic cell population is 

 distributed about a single central, or modal type which can be regarded as 

 characterizing the leukaemia. The modal types of different leukaemias show 

 marked individuality, and are sometimes unique. 



(Hi) The characteristic modal cell-type, and the range of variation about 

 the modal type, are normally maintained through a series of transplant 

 generations. Occasionally, however, a new modal type, closely related to 

 the old, arises. 



(iv) New chromosomal variation attributable to non-disjunction and 

 primary structural change is continuously appearing. The structural 

 changes observed are relatively gross, and reasons were given for supposing 

 that they represent only a part of a continuous series of changes of decreasing 

 magnitude terminating in duplication or deletion of single gene-loci.' 



This is firm evidence that in the established leukaemias there are usually 

 to be found chromosomal changes which can literally be translated chromo- 

 somal-mutations. However, it has yet to be established whether these changes 

 are related to the cause of the leukaemic state or whether they result from it. 

 If they are related to cause, then they should have been pi-esent at the 

 earliest time at which the leukaemia could be recognized in the animal. 

 This has not yet been established in our laboratoiy. Moreover, as Ford and 

 Mole point out, ' There would appear to be two ways in which a distinctive 

 chromosome-set of a primary leukaemia might arise : by progressive, small 

 step by small step, evolution from an original normal cell through the 

 operation of selection on variant types; or by a sudden catastrophic re- 

 arrangement and reassortment of the chromosomes and subsequent minor 

 variation about the new mode. If the latter should be true, carcinogenesis 

 would be the initiation of the catastrophic change and we would still be 

 faced with the problem of discovering what the factors are which determine 

 the change. If, on the other hand, the process should be a slow and pro- 

 gressive one, it would seem to be impossible to define at what stage abnormal 

 but not necessarily pathological cells become frankly neoplastic' 



Certainly major structural lesions of the chromosomes are produced by 

 radiation. Breakage of chromosomes with cross-union translocation has 

 long been recognized as a radiation-induced lesion. Ford et al.^'^ have 

 identified cytologically such a translocation in one of our laboratory stocks 

 (T6) raised by Carter et al^^ from irradiated male mice. These mice contain 

 the translocation in their somatic as well as their germ cells. Nevertheless, 

 the translocation as such is not a determinant of malignancy. We (Barnes 

 et al. unpublished) have maintained myeloid cells of this type as it were in 

 culture in vivo, in successive mice irradiated to destroy their native haemo- 

 poietic tissues and recolonized with myeloid tissue which came originally 

 from a T6 mouse. No leukaemia has been observed in the numerous mice 

 under observation for a period of three years. Furthermore, we have had 

 under observation other lethally irradiated mice, which have been resusci- 

 tated with foreign myeloid tissue, homologous or heterologous, and which 

 some months later have regenerated their haemopoietic tissues from their 



3 21 



