40 MICROSOMAL PARTICLES 



(fig. 2). Work done in our laboratory established that the system corresponds 

 to the endoplasmic reticulum of cultured cells [40], and subsequent observa- 

 tions showed that a number of local differentiations occur within this con- 

 tinuous network which appears to possess, for instance, a rough-surfaced part 

 [40, 41], on account of the attached particles already described, and a smooth- 

 surfaced [40, 41] or agranular [42] part free of such particles. Frequently the 

 elements of the system, particularly its cisternae, show preferred orientation 

 and seem to be disposed parallel to one another at more or less regular intervals, 

 thus forming stacks or piles of various sizes (figs. 1 and 2). Finally, further w. vr k 

 showed that the system varies characteristically from one cell type to another 

 and that these variations affect the total volume of the system, the relative extent 

 of its rough- and smooth-surfaced parts, as well as the extent of preferential 

 orientation encountered within the system [38]. 



The Structural Substrate of Cytoplasmic Basophilia. With the limited infor- 

 mation initially available, it was believed that the endoplasmic reticulum as a 

 whole was the structural substrate of basophilia, but subsequent observations 

 brought forward serious discrepancies between the distribution of the reticulum 

 on one side and that of basophilia on the other. It was found, for instance, that 

 there are cell types with an intensely basophil cytoplasm in which the endo- 

 plasmic reticulum is poorly developed. Such cells, however, have a large popu- 

 lation of small, dense particles, most of them freely scattered in the cytoplasm 

 [43]. The erythroblasts and the undifferentiated cells of rapidly growing 

 epithelia (epithelia of the intestinal crypts, stratum germinativum of the epi- 

 dermis) belong to this category. A converse situation is encountered in mature 

 leucocytes and in seminal epithelia (rat) whose acidophil cytoplasm contains 

 a relatively well developed endoplasmic reticulum, most of it smooth-surfaced, 

 but has only a few small particles, free or attached. 



In all the cases examined, the cytoplasmic component whose distribution 

 matched best that of the affinity for basic dyes appeared to be represented by the 

 small, dense particles. As a result of these findings, in 1953 I advanced [44, 43] 

 the hypothesis that these particles, rather than the membranous material of the 

 endoplasmic reticulum, contained most of the RNA of the cytoplasm, and that 

 they were consequently the sought-for structural substrate of cytoplasmic baso- 

 philia. The hypothesis rested upon the results of a broad survey of various cell 

 types which covered a large number of "test specimens," i.e., cells known for 

 the intensity and characteristic distribution of "basophil substance" in their 

 cytoplasm, as well as cells known for their cytoplasmic acidophilia. The postu- 

 late derived additional support from the fact that at that time small particles in 

 the same size range and containing a large amount of RNA had already been 

 isolated from yeast and bacterial cells [45] by Schachman et al., and from certain 

 mammalian tissues, such as liver and spleen, by Petermann et. al. [46, 47]. 



From the beginning the hypothesis implied that the small particles and the 

 endoplasmic reticulum represent two basically distinct components of the cyto- 

 plasm which may exist and develop independently of each other. Their close 



