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Veterinary Pathology, Vol 33, Issue 2 184-194, Copyright © 1996 by American College of Veterinary Pathologists

ARTICLES

Cellular hyperplasia in rats following continuous intravenous infusion of recombinant human epidermal growth factor

M. A. Breider, M. R. Bleavins, J. F. Reindel, A. W. Gough and F. A. de la Iglesia
Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division of Warner-Lambert Co., Ann Arbor, MI, USA.

In this study, we determined in vivo morphologic effects of continuous intravenous infusion of recombinant human epidermal growth factor (EGF) in adult Wistar rats. The EGF used consisted of the amino acid residues 1-48 of the human 53-amino-acid EGF molecule, purified from transfected Escherichia coli. Doses of 25, 100, or 250 micrograms/kg body weight were administered using Harvard digital syringe infusion pumps for 4 weeks. At necropsy, the submandibular salivary glands, Harderian glands, liver, kidneys (females only), and ovaries were enlarged and urinary bladders were thickened in 100- and 250-micrograms/kg rats. Numerous tissues of the 100- and 250-micrograms/kg rats contained hyperplastic epithelial cells, and selected organs also had mesenchymal cell proliferation. Epithelial proliferation was most pronounced in the trachea, nasal cavity, nasolacrimal duct, tongue, stomach, small intestine, large intestine, urinary tract, salivary gland ducts, and Harderian gland. Periportal hepatocytes were hypertrophic, correlating with increased liver weight. In addition, mesenchymal cell proliferation was evident in the gastric mucosa lamina propria and in heart valves in 100- and 250-micrograms/kg rats. Increased ovarian weight correlated with increased number and size of corpora lutea and an increased incidence of luteal cysts. Continuous systemic exposure of adult Wistar rats to high doses of EGF resulted in generalized epithelial hyperplasia and tissue-selective mesenchymal proliferation.
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This article has been cited by other articles:


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J. W. Henck, J. F. Reindel, and J. A. Anderson
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[Abstract] [Full Text] [PDF]

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J. F. Reindel, A. W. Gough, G. D. Pilcher, W. F. Bobrowski, G. P. Sobocinski, and F. A. De La Iglesia
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J. F. Reindel, G. D. Pilcher, A. W. Gough, J. R. Haskins, and F. A. De La Iglesia
Recombinant Human Epidermal Growth Factor1-48-Induced Structural Changes in the Digestive Tract of Cynomolgus Monkeys (Macaca fascicularis)
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[Abstract] [PDF]


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Copyright © 1996 by the American College of Veterinary Pathologists.