LEUKAEMOGENESIS— EOLE OF VIRUSES AND 

 CYTOLOGICAL ASPECTS 



ARTHUR C. UPTON 



Biology Division, Oak Ridge National Laboratory,^ Oak Ridge, Tennessee, U.S.A. 



SUMMARY 



1. The presence of filterable leukaemogenic agents in the tissues of irradiated mice 

 and in those with radiogenic leukaemia implicates viral mechanisms iti radiation 

 leukaemogenesis. 



2. The respective roles of radiation and virus in leukaemogenesis cannot yet be 

 defined, but the available data suggest that murine leukaemia evolves through a multi- 

 stage process requiring the interaction of virus, host cells, and host. In such a complex 

 system, radiation may act in several ways, one of them being to activate a latent 

 leukaemogenic vii'us. The basis for the relatively long induction period, however, in 

 spontaneous and radiation leukaemogenesis remains an enigma. 



3. Evidence pomts to the possibility that the same virus may induce different haema- 

 tologic forms of leukaemia in irradiated and non-irradiated individuals, depending on the 

 constitution and physiological condition of the host. 



4. The occurrence of specific abnormalities of a single human chromosome (probably 

 No. 21) in clu-onic myelogenous leukaemia and in Down's syndrome, which carries an 

 increased propensity to leukaemia, suggests that cytogenetic changes may be of causal 

 significance m human leukaemogenesis. Data on the frequency of spontaneous and 

 radiation-induced chromosome breakage, however, argue against a simple one-break 

 aetiologic mechanism in the pathogenesis of the disease. 



5. On the basis of tracer studies, the growth of leukaemia cells is not characterized 

 by abnormally rapid cell division. Precise details of the kinetics of leukaemic growth 

 remain, however, to be elucidated. 



Although leukaemia was one of the first neoplasms recognized as a potential 

 hazard of ionizing irradiation (von Jagie etal., 1911), it was not until recently 

 considered possible that a small radiation dose might carry a finite leukaemo- 

 genic risk. The available data do not yet provide a clear picture of the relation 

 between incidence of leukaemia and dose, nor of the mechanism of leukaemia 

 induction (see Upton, 1961), but several recent advances towards an under- 

 standing of leukaemogenesis are worth noting. These include: (1) the observa- 

 tion that some lymphosarcomas may be induced by radiation in the mouse 

 thymus without irradiation of the thymus itself, (2) the discovery that certain 

 radiogenic leukaemias yield filterable leukaemogenic agents, suggesting that 

 viruses are involved in their pathogenesis, and (3) the disclosure that specific 

 human chromosomal abnormalities are associated with chronic myelogenous 



t Operated by Union Carbide Corporation for the United States Atomic Energy Commission. 



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