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The effects of sublethal amounts of the cationic dye, neutral red, upon the structure of pancreatic exocrine cells, and upon the mitochondria of renal distal tubule cells, have been studied with the electron microscope. It was found that neutral red is a cytoplasmic toxin which causes reproducible and characteristic changes in the ergastoplasm, the zymogen granules, the mitochondria, and possibly in the Golgi complex. Ergastoplasmic membranes and granules and zymogen granules lose definition and become continuous with the cytoplasmic matrix. Mitochondria lose their internal folds, develop vacuoles which contain a solution of neutral red in high concentration, and form the nidus for the development of sudanophilic, argyrophilic, osmiophilic inclusions which appear in the cytoplasm after neutral red administration. Golgi granules, one of the three elements of the Golgi complex, appear to increase in number and to be scattered more widely through the cytoplasm than is normal. No consistent changes were found in the cell membrane or nucleus. The ability of the mitochondria to concentrate the cation, neutral red, taken with its well known ability to concentrate the cationic Janus dyes and methylene blue, and its probable role in concentrating those cationic dyes which have been used to demonstrate the "vacuome," is interpreted to signify that one of the functions of mitochondria may be to concentrate intracellar cations.

INTRACELLULAR CHANGES DUE TO NEUTRAL RED AS REVEALED IN THE PANCREAS AND KIDNEY OF THE MOUSE BY THE ELECTRON MICROSCOPE