The appearance and degradation of specific hepatocellular cytoplasmic inclusion bodies in rat liver due to D-galactosamine

Abstract
One of the most sensitive and specific signs of the galactosamine GalN effect upon the rat liver cell is the appearance of PAS[periodic acid-Schiff]-positive and diastase-resistant granules within the cytoplasm of hepatocytes. Light microscopic, histochemical, biochemical and EM findings reveal that the appearance of these ADB (atypical dense bodies) depends upon a working glycogen metabolism at the time of GaIN treatment. The ADB are composed of particles resembling, due to shape and size, ribosomes and .beta. particles of glycogen. Most of them are surrounded by the rER [rough endoplasmic reticulum], but they are never enclosed by a limiting membrane. Due to sequential changes they can be classified into 3 types: the early, the intermediate and the late. In 7 experiments it was shown that the appearance of the ADB depends upon the time and dosage after GalN treatment. They occur even if an additional treatment with galactose or uridine prevents the liver from the features of hepatitis, as shown in the livers of newborn animals up to 3 wk of age. The histochemical response against various glucosidases, hexosaminidases, pronase and RNase as well as against various fixatives indicates that ADB are composed of at least 2 different constituents, the former being RNase-sensitive and visible with routine light microscopic staining procedures, and the latter being RNA-resistant, PAS-positive and invisible after staining with H and E or toluidine blue. The latter is diastase-resistant, suggesting that this portion of ADB does not represent the usual glycoproteins but some abnormal metabolite of glycogen. The ADB can be detected with maximal accumulation in the cytoplasm of hepatocytes at that time when the glycogen content determined in the liver homogenate by biochemical methods is greatly reduced.

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