HISTOLOGICAL CHANGES 



50 anaphases were analysed in each specimen. The figures in parentheses indicate 

 the number of mice which were investigated. 



Betz : Gerebtzoff a signale des differences dans I'extension des degenerescences 

 cellulaires dans la rate de souris irradiees et de souris irradiees apres protection par 

 la cysteinamine. Je voudrais lui demander si ces differences atteignent au meme 

 titre les tissus myeloi'des et les tissus lymphoides de cet organe. 



M. A. Gerebtzoff : I did not study, from the quantitative point of view, the 

 difference in reaction between lymphoid and myeloid tissues in spleen, but it appears 

 that the protection of myeloid tissue by cysteamine is stronger than the protection 

 of lymphoid tissue. 



Harvey M. Patt : Our studies*' * of the adrenal response to X-irradiation would 

 seem to support, at least in part, the interpretation advanced by Betz. The data 

 presented by Bacq are essentially a confirmation of earlier work. Ionizing radia- 

 tions, in common with other noxious stimuli, induce changes that are presumed to 

 reflect an increased demand for the adrenal hormones. The functional response of 

 the adrenals is mediated by the pituitary and closely resembles that seen following 

 a host of injuries. While the early decrease in adrenal lipids is probably indicative 

 of an increased requirement for cortical secretions, the rise in adrenal cholesterol in 

 the rat several days after median lethal irradiation may represent over-stimulation in 

 excess of cortical hormone demand. That the elevated cholesterol is not a result 

 of adrenal exhaustion is suggested by its absence with higher dosages. Although 

 adrenal lipids are usually depleted before death, it is not known whether this is a 

 cause or an effect of the more terminal events. It is particularly noteworthy that 

 Edwards and Sommers'" were unable to detect any fundamental difference in 

 radiation reactions as a consequence of adrenalectomy of shielded or irradiated 

 parabionts and that Schneider et al^^ observed that the adrenals of irradiated rats 

 were capable of sustaining non-irradiated adrenalectomized parabionts. Absence 

 of the adrenals did not compromise protection of irradiated animals by parabiosis. 

 These results strongly suggest that the adrenals of lethally irradiated rats suffer no 

 basic impairment. 



Turning to the mechanism of protection by ^-mercaptoethylamine, there is, at 

 present, no direct evidence and little reason to assume that the effect is a consequence 

 of the protection of a specific restoration factor. Arguments for the latter fail to 

 consider a very basic matter, namely the relative radio-sensitivities for different 

 morphological and functional responses. We may note in particular (/) the difficulty 

 of differentiating the extent of initial injury in the lethal range by ordinary histological 

 criteria, (2) that many responses, e.g. lymphoid involution, are related more to the 

 radiation dose than to the lethal or morbid effect, (3) that near maximal initial 

 effects may occur at dosages considerably below those required for acute lethality. 

 It is possible under appropriate experimental conditions to demonstrate prevention 

 of injury in a variety of systems by agents such as p-mercaptoethylamine and cysteine. 

 The sparing of comparatively few cells initially might exert a profound influence on 

 the recovery pattern of the tissue as a whole. It should be remarked that it is neces- 

 sary to consider another matter in interpretation of protective phenomena, namely, 

 the temporal and spatial distribution of a given agent in the biological system. 

 Localization of p-mercaptoethylamine to specific sites, as discussed by Eldjarn*, 

 might preclude a more generalized protective action in the animal. 



Bacq has alluded to the possibility that the effects of fi-mercaptoethylamine on 

 the one hand and of spleen shielding and homogenates on the other may be related. 

 This is so to the extent that both modify the acute lethal action. In fact, cysteine 

 has been shown by Simmons et al to synergize with spleen shielding. This, however, 

 does not imply necessarily that the basic mechanisms underlying the protection are 



* See page 1 16. 



312 



