PHYSICAL AND BIOLOGICAL FACTORS 921 



molecules are of critical importance in the cell economy since most of 

 these would be water molecules. These considerations raise the question 

 of the localization and amplification of the early critical events. 

 Although amplification could be accomplished by inactivation of genes or 

 enzymes, by some disturbance in the synthesis or assembly of essential 

 substrates, or by the formation of toxic substances, the nature of the 

 early physicochemical events is obscure and poses the most formidable 

 problem in radiobiology. 



Two main concepts of radiation effects on living systems have been 

 formulated. These are described most frequently as the theories of 

 direct and indirect action and have been presented in some detail by 

 Lea (1946) and others. Direct action postulates that ionization occurs in 

 specific molecules that constitute a sensitive region or vital target. This 

 idea in its classical sense is compatible with the single-hit type of effect 

 that is characterized by its exponential relation to radiation dosage, its 

 independence of dosage rate, and the inverse relation between its effi- 

 ciency and ion density. It is perhaps best expressed in the effects on 

 dried biological materials. 



Both the direct and indirect concepts assume that chemical changes are 

 induced by ionizing radiation, either by the alteration or inactivation of 

 important molecular species or by the production of substances that 

 influence cell metabolism (Zirkle, 1949). The indirect effect assumes 

 that the initial chemical changes are due to highly reactive substances, 

 mainly oxidants, that are formed at random in the aqueous environment 

 and subsequently react with critical entities. Thus, localization of an 

 effect within the living system is secondary and depends upon the nature 

 of the acceptors as well as upon the original distribution of ions, the 

 number of reactive substances formed, and the kinetics of their diffusion. 

 The indirect type of action is dose rate dependent and varies, generally, 

 directly with ion density. Organic molecules may, therefore, be modified 

 by direct ionization and excitation or by reaction with the decomposi- 

 tion products of water. While it has not been possible to demonstrate 

 these phenomena directly in irradiated biological material, there is 

 sufficient circumstantial evidence to justify the assumption that they 

 occur. 



Perhaps the outstanding characteristic of radiobiological responses is 

 their diversity, a not unreasonable situation when we consider that the 

 radiant energy is absorbed at random in a heterogeneous and highly 

 integrated system. Thus it is not surprising that many different effects 

 are observed even on the cellular level and that not all these are in direct 

 consequence of the radiation. It is probable that many of the seemingly 

 discordant observations found in the literature are real and merely reflect 

 the inherent complexity of the chain of events concerned in the radiation 

 response and that of the responding organism. 



