210 - "ATOMIC MEDICINE 9.5 Pathogenesis of Radiation Injury — Numerous theories have been advanced to explain the biological effeets of ionizing radiations. Only those theories which mayhelp to understand the pathogenesis of total body radiation and which mayindicate a possible therapeutic approach will be considered in this chapter. It is probable that the primary interaction between radiation and tissue may involve either direct “hits” on biochemical molecules, or ‘indirect effects” on such molecules mediated through radicals produced by interaction of the radiation with water and other chemical substances in the tissue. These primary phenomena will not be considered in detail here. For purposes of discussion, only those mechanismsat the biochemical or higher level that have been considered to play a role in initiating and continuing the acute radiation syndrome will be considered. Several possible mechanisms that have been considered to be contributory are listed and discussed below, even though some of these are currently believed to play a minor, if any, role in the development of the signs and symptomsobserved. Enzymeinhibition; activated radicals, 2. Alterations in cell membrane permeability, 3. Generalized protein denaturation, + Inhibition of mitosis; chromosome changes, 5 . Production and circulation of toxins 6. Adrenal cortical insufficiency, 7. Pancytopenia and its sequelae. The syndrome is obviously the result of disturbances in the homeostasis of the animal produced by cellular injury of varying degrees in different organ systems. The fifth to seventh mechanisms are attempts to explain the clinical syndrome at a mammalian level. The seventh mechanism probably the result of the fourth, will explain most of the gross clinical and pathological observations seen in animals dying in the lethal range. 9.5.1 Enzyme Inhibition. The concept of enzyme inhibition has been carefully and extensively studied by Barron and associates. Initially it was thought that enzyme inhibition was not considered important because the doses necessary to inactivate concentrated enzyme solutions were 10 to 1000 times greater than those that seriously injure living tissues. The present status of the enzyme inhibition concept may be summarized as follows: As a result of the work of Fricke, 1934, and of Dale, 1943, and others, it has been shown that in dilute solutions the number of molecules brought into reaction is proportional to the number of ions produced in the solution, and is independent of the concentration of the solution. This led to the concept that the action of the radiation is not primarily ou the dissolved = Reet pre -