CELLULAR HYPERPLASIA IN RATS FOLLOWING CONTINUOUS INTRAVENOUS-INFUSION OF RECOMBINANT HUMAN EPIDERMAL GROWTH-FACTOR

In this study, we determined in vivo morphologic effects of continuous intravenous infusion of recombinant human epidermal growth factor (EG F) in adult Wistar rats. The EGF used consisted of the amino acid resi dues 1-48 of the human 53-amino-acid EGF molecule, purified from trans fected Escherichia coli. Doses of 25, 100, or 250 mu g/kg body weight were administered using Harvard digital syringe infusion pumps for 4 w eeks. 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-mu g/kg rats. Numerous tissue s of the 100- and 250-mu g/kg rats contained hyperplastic epithelial c ells, and selected organs also had mesenchymal cell proliferation. Epi thelial 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 weigh t. In addition, mesenchymal cell proliferation was evident in the gast ric mucosa lamina propria and in heart valves in 100- and 250-mu g/kg rats. Increased ovarian weight correlated with increased number and si ze of corpora lutea and an increased incidence of luteal cysts. Contin uous systemic exposure of adult Wistar rats to high doses of EGF resul ted in generalized epithelial hyperplasia and tissue-selective mesench ymal proliferation.