SSS EA AAEe he QR SekaSaal al ye RADIATION INJURY: ITs PATHOUD N Eels AND THERAPY Pil substance, but on the solvent. The activation of water consists of the production of highly reactive oxidizing substances (OH, HeO. and other complexes) as the result of ionizing radiation. Phe active products pre- sumably oxidize the sulfhydrvl groups Sil) of many enzymes to the en- zymatically inactive disulfide form. This inactivation is generally reversible in the lower dose range. With larger amounts of radiation, the enzyme inhibition is also produced by protein enzyme denaturation by direct tupture of chemical bonds. This type of denaturation is irreversible. Reversible enzyme inhibition may play a part in the initiation of the svn- drome of radiation illness, particularly in the lethal range, tut is probably not the only and may not be the most important initiating mechanism. Recently Pajewski and Pauly have studied the effects of radiation on enzymes in impure solution, and finds the doses required for inactivation to be quite high. This may be explained on the basis that while enzymes in pure dilute solution may interact with essentizally all radicals produced in the water, in the presence of relatively inert competing substances, very high doses maybe required forsignificant inactivation. Thus while enzyme inhibition may play a role in producing damage, there is at present no conclusive proof that this mechanismts of major importance in producing the acute radiation syndrome. 9.5.2 Alterations in the Permeability of Cell Afembranes have been postulated. Absorption of water and vacuole formation can be observed within nuclei. This mayresult in alterations in the permeability of cell membranes or an increased intranuclear osmotie pressure (Failla). 9.5.3 Denaturation of Proteins. In general, in addition to the protein enzymes already considered, denaturation has been postulated as being responsible for some of the phenomena that are observed. Denaturation is known to oecur at higher dose ranges; however, it appears unlikely that it plays asignificant role at dose levels of most interest hiologically. 9.5.4 Inhibition of Afitosis; Chromosome Changes. Mitotic inhibition occurs at relatively low dose levels.Apparent recovery mayresult, and the mitotic index may return to normal within a short time (Fhednercf al.). However, even at doses as low as 100 or 200 r, a large numberof mitotic figures may show obvious abnormalities (Puck; Bender; Flhedner, Bond, Cronkite). These abnormalities may range in severity from gross disruption of the chromosome pattern with fragmentation of individual chromosomes to chromosome “stickiness,” and undoubtedly to damage too subtle for detection by cytological means. The cell so affected may die essentially immediately, it may fail to divide and become a “giant” cell, or it may be able to go through a limited number of subsequent divisions before al] progeny die. The net result is that the proliferative potential of organs composed of rapidly dividing cells is reduced, and thus celhilarityis reduced.