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Ultrastructural and Biochemical Changes Associated with Pyrrolizidine-induced Hepatic Megalocytosis¹

Department of Pathology and Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53706

Rats were fed a diet containing from 0.02 to 0.08% ground Crotalaria spectabilis seed for 8 months to evaluate the biochemical and ultrastructural changes that occurred in the livers of chronically intoxicated rats that developed megalohepatocytosis. These rats had small irregularly shaped livers with disrupted architectural patterns. Microscopically, the livers were composed primarily of megalohepatocytes 2.5 times the size of the normal hepatocytes, hyperplastic bile ducts, and regenerative nodules. The ultrastructural features and biochemical changes of these affected livers were similar to those reported in naturally occurring and experimentally induced hepatomas. The megalohepatocytes contained enlarged, irregularly shaped nuclei. Numerous organelle-filled invaginations of the nuclear membrane protruded into the nucleoplasm. Some invaginations separated from the nuclear membrane and formed membrane-enclosed nuclear inclusions. Other partially enclosed invaginations resulted in a mixture of nuclear and cytoplasmic constituents. The nucleolar components were abundant and were dispersed throughout the nucleoplasm. Alterations in the cytoplasmic organelles of the megalohepatocytes included a decrease and a morphological modification of the rough endoplasmic reticulum. Lamellar arrays of smooth endoplasmic reticulum filled large portions of the cytoplasm. An increase in the size and distribution of the Golgi complex and a reduction in attached ribosomes and glycogen granules were apparent. The RNA and nitrogen levels of the affected livers were of the same magnitude as the controls, while the DNA was increased to 200%.

¹ This research was supported in part by USPHS Grant HE 10941. Portions of this study were presented at the 66th Annual Meeting of the American Association of Pathologists and Bacteriologists, March 9–11, 1969, San Francisco, Calif.

Received 11/18/69. Accepted 3/ 3/70.

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