INVITRO MODEL OF PANCREATIC CARCINOMA - MORPHOLOGY AND INVIVO GROWTH

Abstract

Pancreas rudiments from 13 day rat embryos were cultured in the presence of dimethylnitrosamine (DMN) for up to 10 wk. Pancreas morphogenesis and differentiation occurred during the 1st wk of culture. Acinar cell degeneration and necrosis began on the 5th day of culture and resulted in almost complete loss of acinar cells, islet cells and fibroblasts by the end of the 3rd wk. This was associated with proliferation of cells without zymogen granules (centroacinar, ductal or undifferentiated). These cells formed glandular structures which extended to the surface of the explant. By the end of the 4th wk, explants resembled ductal hyperplasia with foci of carcinoma in situ. The distribution pattern of neoplasia in 343 explants examined after 10 wk of DMN treatment was as follows: 79% resembled ductal cell carcinoma; 9%, ductal hyperplasia and 3% acinar cell carcinoma. Nude mice injected with cell suspensions prepared from 10 wk old culture developed subcutaneous nodules. These nodules resembled duct cell carcinoma with desmoplastic reaction.