Nucleolar alterations induced by 4-aminopyrazolo(3,4-d)pyrimidine in adrenal cortex and liver cells of rat.

The nucleolar ultrastructural changes produced in adrenal zona fasciculata cells and hepatocytes of rats by 4-aminopyrazolo(3,4-d) pyrimidine (4-APP), an inhibitor of the lipoprotein synthesis, are described. Male rats were injected intraperitoneally for three consecutive days with 4-APP in sodium phosphate buffer (50 mg/Kg/day). On the 4th day, the animals were sacrificed and their adrenals and liver were processed for EM. The nucleoli of the adrenal zona fasciculata cells showed nucleolar fragmentation with loss of their normal reticular appearance, separation of fibrillar and granular components, extensive vacuolization and evidence of fibrillar centers. The hepatocyte nucleoli also exhibited fragmentation. These changes seem to be the morphological counterpart of alterations in rRNA synthesis and processing, since 4-APP inhibits "de novo" purine synthesis and thus interferes with its incorporation into RNA and DNA.