LYSOSOMES, A NI.W CROl-p OI' CVTOPI.ASM IC PARTICLES 1^5 



According to CJoutier-Pirollc (40), tins UcalinciU causes a lahili/.alioii ol the 

 linkage betwen acid deoxyribonuclcasc and particles in rat spleen. No increase in 

 the unsedimentable activities ot he[i.itic lysosomal enzymes in li\er nor ol the 

 acid phosphatase, or cathepsin of spleen has, however, been observetl by Mrs. 

 Deckers-Passau (unpublished observations) in rats killetl 1 or 12 hours alter 

 having been subjected to a dose ot 1000 r. 



Mechanism of Lysosome Rupture in Intact Cells. Several of the phenomena dis- 

 cussed in the previous sections raise the problem of the nature of the mecha- 

 nisms, either physiological or pathological, whereby lysosomes may become 

 ruptured in living, dying or dead cells. Our only direct piece of information 

 bearing on this point is provided by some experiments on liver slices showing 

 that the rupture of lysosomes occurs more rapidly in the absence than in the 

 presence of oxygen. Most of the observations described in the [irevious section 

 could be related to partial or total anoxia, and the importance of this factor in 

 the pathogenesis of necrosis has been repeatedly emphasized (see 17, 45). 



As to how anoxia may affect the lysosomal membrane, one may consider sev- 

 eral possibilities: /) the membrane is a dynamic structure which is continuously 

 rebuilt with the help of oxidative energy; 2) the integrity of the membrane de- 

 pends on the maintenance of some of its components in the oxidized state; 

 ^) anoxia releases one or more enzymes which break down the membrane. 



With respect to the second possibility, we have not found any difference in 

 the stability of isolated particles whether incubated aerobically or anaerobically. 

 However, more complex phenomena may be involved and the results of Green 

 and Mazur(4i), who have described an anoxic release of ferritin apparently 

 mediated by uric acid and other purines, deserve mentioning in view of the 

 possible presence of ferritin and uricase in the lysosomal matrix. As to the third 

 possibility, a particularly simple mechanism could be set up by the anoxic 

 lowering of the intracellular pH, which might be sufficient to accelerate a 

 catheptic rupture of the lysosomal membrane from within. The autolysis of the 

 particles has indeed been shown to be strongly pH-dependent in vitro {2). It is 

 interesting that other causes of acidosis, such as ketosis, could have a similar 

 effect. In addition to anoxia, the possible involvement of rupturing agents, such 

 as carbon tetrachloride or bile salts, should also be mentioned. 



CONCLUSION 



The principal aim of the preceding account has been to review and to delineate 

 as clearly as possible the experimental facts which have led to the formulation of 

 the lysosome concept. The possible relationship of the lysosome particles with 

 mitochondria, although postulated by many authors on the basis of morpho- 

 logical observations, has not been discussed here; firstly, because the morpho- 

 logical identification of lysosomes has not yet been made with certainty; and. 



