Bae et gga cain A ee ae OE NO bo RADIATION INJURY: Tis PATHOGENDSIS AND THE RAPS 22] One compound, SB) d-armino-ethylisothiomponeun: BrP Br ART has shown some protuisc ti this regard because of its high deeree of eflectiseness und low tovieity when given orally to rodents. These favorable qual ties have been less pronounced ti higher species; however, the mechanistns by which preprotective agents uet are not clear and are controversial, Hypoxia and hypoxia-inducing agents are effective presumably by a reduction in the formation of free radicals, and it is not clear how many of the protective agents may act at least In part ea this mechanism. A number of compounds are prestuned to act through a free radical scavengIng mechanisin, i.e., by conipeting for intracellular free radicals produced by the radiation. Thiol compounds are known to have a great affinity for free radivals. These mechanisms would not explain protection against the direct effects of radiation, although it is not established what proportion of the total effect is direct or indirect under various circumstances. Some agents apparently protect by induction of metabolic changes; others presumably by restoration of injury in the primary target. 9.7.5 Shielding Effects (also xee section 9.8.2). The prototype of shielding experiments was initiated by Chiari who in 1912 demonstrated that bone marrow of the rabbit when transplanted to the spleen would growonlyif the spleen were shielded and the rest of the animal were irradiated. Fabriclus-Méller clearly demonstrated that shielding of portions of the skeleton prevented the fall in blood platelets and hemorrhage from doses which uniformly killed his unshielded animals. Chrom (1935) reported a series of experiments on shielding portions of the abdomen and its influence on phagocytosis of bacteria. The technique of shielding has been elaborated and exploited by Jacobson ef al. in a large series of articles in the past few years. Jacobson and his group have shown a very striking protection of mice to an approximate 100 per cent lethal dose of radiation when the mouse spleen* and the other organs are shielded with lead. Shielding of these organs resulted in a very marked increase in rate of hemopuietic regeneration. ; Other shielding experiments have demonstrated protection; for example, shielding of the adrenals (edelmann) and the head (Allen ef al.). Bondef al. have shown that the time sequence, survival time and nature of death is different when the abdomenis shielded than when the skeleton is shielded. Tt requires a larger dose in r to kill when the abdomen is shielded and le=s when only the abdomen is expoxed, and thus a good part of the skeleton is shielded. Abdomen-exposed animals die more quickly. Protection is eonferred if one-half of the bodyonlyis exposed, followed in a matter of min* The mouse spleen shows extensive myelopoiesis under normal conditions; hence the protective effect of splenic shielding in the mouse is not necessarily something that is unique to the splenic tissue per sc.