174 UPTON, CONKLIN, MCDONALD, AND CHRISTENBERRi' 



From these observations, it may be inferred that oncogenesis constitutes 

 but one of many late somatic effects of radiomimetic chemicals. As important 

 as oncogenesis are effects on the severity and age distribution of non-neoplastic 

 changes, which mimic the effects of radiation. Whether both classes of effects 

 may reflect common mechanisms cannot be decided without further informa- 

 tion. It is tempting, however, to interpret them in terms of chromosomal 

 and genetic hypotheses of carcinogenesis and ageing. Viewed in this context, 

 the greater life-shortenmg effectiveness of TEM, as compared with HN2, 

 may derive from the greater potency of TEM as a mutagen and chromosome- 

 breaking agent (Cattanach, 1957). 



Without speculating further about the mechanisms of the effects reported 

 herein, we may envisage new approaches to the study of carcinogenesis and 

 ageing through comparative studies of radiomimetic chemicals and radiation. 

 Systematic appHcation of radiomimetic agents varying m chemical specificity 

 may provide added insight into the molecular basis of effects appearing 

 months or years after exposure. The significance of such comparisons must be 

 interpreted with reservation, however, in view of the possibility that the 

 same functional or morphological lesion may come about through diverse 

 biochemical mechanisms (Koller and Casarini, 1952), 



ACKNOWLEDGMENTS 



We are grateful to R. C. von Borstel for suggesting the use of TEM and for 

 helpful discussion of the experiment, to M. A. Kastenbaum and J. F. Parham 

 for data processmg, and to W. D. Gude and T. Mack for histologic assistance. 



EEFEKENCES 



Alexander, P., and Connell, D. I. (1960). Radiation Res. 12, 38. 



Cattanach, B. M. (1957). Nature, Lond. 180, 1364. 



Curtis, H. J., and Gebhakd, K. L. (1959). In "Progress in Nuclear Energy Series VI Vol. 



2._Biological Sciences", p. 210. Pergamon Press, London. 

 Koller, P. C, and Casarini, A. (1952). Brit. J. Cancer 6, 173. 

 Stevenson, K. G., and Curtis, H. J. (1961). Radiation Res. 15, 774. 

 Upton, A. C, Kemball, A. W., Furth, J., Christenberry, K. W., and Benedict, 



W. H. (1960). Cancer Res. 20, No. 8 (Part 2), pp. 1-62. 



DISCUSSION 



ALEXANDER: I just Wanted to raise the point about these lung adenomas. Don't they 

 occur very late m hfe? These different incidences you show mean that the radio - 

 mimetics and the X-rays are both carcinogenic in so far as they induced lung adenomas 

 but this reduction in the X-ray cases may be because the animals didn't Uve long enough 

 to get the lung adenomas. 



