ISLET CELLS AS A COMPONENT OF PANCREATIC DUCTAL NEOPLASMS .1. EXPERIMENTAL-STUDY - DUCTULAR CELLS, INCLUDING ISLET CELL PRECURSORS, AS PRIMARY PROGENITOR CELLS OF TUMORS

Abstract

The ductular complex of the Syrian hamster pancreas represents a system of conduits which encompasses intercalated (intralobular), periinsular and intrainsular ductules. The intercalated (intralobular) ductules comprise centroacinar and intercalated cells. A meshwork of small ductules (invisible by usual histologic procedures) surrounds islets (periinsular ductules) and extends in the form of often ramified tiny channels within the islet (intrainsular ductules). Although the function of the latter ductules is obscure, their cells seem to make up 1 of the undifferentiated cellular units of the pancreas, and as such are also the progenitors of .beta.-cells of the islets (islet cell precursor = IP). Systematic histologic examination of the pancreas in this species treated with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine indicated that ductular cells, especially those of periinsular and intrainsular origin, are the most responsive to this carcinogen. The neoplastic process was initiated with hyperplasia of intercalated (intralobular) ductular and interlobular ductal cells associated with newly formed islets (nesidioblastosis). This process was followed by excess formation of mature, but especially of immature islet cells and their precursors (IP) in the islet periphery, as well as the appearance, distention and multiplication of periinsular and, particularly, intrainsular ductules. The hyperplasia, metaplasia and malignant alteration of these periinsular and intrainsular ductules (including IP) and to a lesser degree, intercalated ductules indicated their histogenetic relationship and their potency for reproducing embryonic tissue on carcinogenic stimulus. The similarity of some induced lesions to diabetes was emphasized.