SYSTEMIC TREATMENT WITH EPIDERMAL GROWTH-FACTOR IN PIGS INDUCES DUCTAL PROLIFERATIONS IN THE PANCREAS

Background & Aims: Epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and the EGF receptor are often overexpressed in chronic pancreatitis and in malignant pancreatic growth. Transgeni c mice overexpressing TGF-alpha develop tissue changes in the pancreas resembling changes found in chronic pancreatitis, The effects of syst emic treatment with EGF on the porcine pancreas were investigated in t his study, Methods: Mature Goettingen minipigs were treated with solve nt (n = 5), EGF (30 mu g.kg(-1).day(-1); n = 6) for 4 weeks, or EGF (3 0 mu g.kg(-1).day(-1); n = 5) for 5 weeks followed by 3 weeks of recov ery, Pancreata were studied by routine histological examination and el ectron microscopy and were immunostained for proliferating cell nuclea r antigen (PCNA), Results: In the EGF-treated animals, mainly larger i nterlobular ducts of the pancreas appeared to be considerably hyperpla stic, with an increased number of nuclei that stained for PCNA, The ep ithelia of these ducts were increased in height, with accumulations of glycoconjugates in the columnar cells and in an increased number of g oblet cells, Conclusions: A new approach to experimentally induced hyp erplastic changes of the excretory ducts of the pancreas is presented, Because ductal changes with glycoconjugate accumulations are common f eatures of chronic pancreatitis and pancreatic cancer, the findings ma y be relevant to the pathogeneses of these conditions.