920 RADIATION BIOLOGY 



action of radiation on different parts of the same cell and on different 

 cells; the relation between differentiation, mitotic activity, and radio- 

 sensitivity; the importance of intensity-duration considerations in the 

 radiation effect; and the latency of most biological responses. 



Although many of the important effects of ionizing radiation were 

 reported over 25 years ago, radiation dosimetry unfortunately did not 

 keep pace with the biological approach. Advances in radiation physics 

 and the availability of many different sources of radiation, culminating in 

 the development of the cyclotron and other accelerators and the chain 

 reactor, have now made possible a quantitative reinvestigation and 

 amplification of the earlier qualitative observations and have, in addition, 

 opened new avenues for investigation. It is our intention to present a 

 comprehensive, though not necessarily encyclopedic, appraisal of the 

 pathological physiology of radiation injury in the mammalian organism. 

 The existence of several excellent reviews of the early literature has 

 greatly simplified our task. Although we have drawn upon some early 

 observations, our source material has largely been restricted to the more 

 recent papers and to the Manhattan Project and Atomic Energy Com- 

 mission documents. For convenience, the presentation has been divided 

 into two parts, the first being concerned with the physical and biological 

 factors in radiation action and the second with the specific aspects of the 

 physiology of radiation injury. 



NATURE OF THE BIOLOGICAL RESPONSE TO RADIATION 



High-energy radiations dissipate their energy in tissue by ionization 

 and excitation. The dependence of biological effectiveness upon the 

 specific ionization or ion density of a particular radiation lends strong 

 support to the idea that its action is related in some manner to direct 

 local release of energy, presumably through ejection of electrons from 

 the atoms through which it passes. While the role of excitation is not 

 well defined, it may constitute an important secondary, if not primary, 

 process. An interesting aspect of the energy absorption is the relatively 

 small absolute amount that is required to produce widespread effects. 

 One thousand roentgens, a lethal dose for most mammals, corresponds to 

 an energy absorption of only 2 X 10- 3 calorie per gram. We may 

 examine the problem in another way by computing the fraction of 

 molecules within a cell that is likely to be modified as a direct result of 

 the radiation. In a cell containing about 10 14 molecules, 1000 r would 

 be expected to ionize only 10 7 molecules. Although it is likely that 

 many more molecules will be affected indirectly in consequence of the 

 energy transformations resulting from the absorption of radiation, the 

 total number of altered molecules is probably a small fraction of those 

 present within a cell. It would seem, moreover, that not all the damaged 



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