Effects of dimethylnitrosamine on organ-cultured adult human pancreas

Portions of adult human pancreas from 20 donors were organ-cultured in a chemically defined medium in the absence or presence of DMNA for up to 12 weeks. In the absence of DMNA, necrosis of some acini occurred during the first week, while some clusters of well-preserved acini were maintained for up to 3 weeks. Proliferation of the epithelial linings of main and smaller ducts and ductules was noted during the first 2 weeks of culture. Ductal epitheliums thereafter showed some degeneration but remained viable during the 12 weeks of culture. In contrast to controls, the DMNA-treated explants showed better preservation of both acinar and ductal cells. DMNA induced both ductal hyperplasia and atypia of the epithelial linings of main ducts, smaller ducts, and ductules within 6 weeks, and carcinoma by the tenth week of culture. At the end of the first week cells devoid of zymogen within the acinar complex proliferated and progressively replaced necrotic cells. During the ninth and tenth weeks, foci of atypical cells developed among these cells. Cells derived from 10-week-old DMNA-treated explants produced multiple nodules of carcinoma when injected subcutaneously into nude mice.