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Ultrastructural Changes in Hepatocellular Rough Endoplasmic Reticulum in Rats Given a Pyrimidine Derivative

Published online by Cambridge University Press:  02 July 2020

Beverly E. Maleeff
Affiliation:
SmithKline Beecham Pharmaceuticals, Department of Toxicology-US, King of Prussia, PA
Stephen J. Newsholme
Affiliation:
SmithKline Beecham Pharmaceuticals, Department of Toxicology-US, King of Prussia, PA
Timothy K. Hart
Affiliation:
SmithKline Beecham Pharmaceuticals, Department of Toxicology-US, King of Prussia, PA
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Extract

Hepatomegaly, characterized by increased liver weight due to hyperplasia or hypertrophy, can be induced in many species by various drugs or environmental toxins. In rats, hepatomegaly is more usually associated with increases of smooth endoplasmic reticulum in hepatocytes and the associated induction of cytochrome P450 enzymes or with hepatocellular peroxisomal proliferation. In this study, a substituted pyrimidine derivative given to rats resulted in hepatomegaly with an unusual selective increase in hepatocellular rough endoplasmic reticulum (RER).

Female Sprague-Dawley rats were given repeated oral doses of a substituted pyrimidine derivative for 28 consecutive days. Livers were collected at necropsy, weighed, fixed in 10% neutral buffered formalin and processed to paraffin sections stained with hematoxylin and eosin (H&E) for light microscopic evaluation. Portions of formalin-fixed liver were transferred to buffered 2.5% glutaraldehyde for ultrastructural evaluation. Specimens were processed into epoxy resin and thin sections were examined with a JEOL 1200EX transmission electron microscope.

Type
Pathology
Copyright
Copyright © Microscopy Society of America

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