Two populations of cells with differing proliferative capacities in atypical acinar cell foci induced by 4-hydroxyaminoquinoline-1-oxide in the rat pancreas

A single intravenous injection of 4-hydroxyaminoquinoline-1-oxide in male Wistar rats at a dose of 6 mg. per kg. of body weight induced atypical acinar cell foci in 100 per cent of the animals. Atypical acinar cell foci could be classified histologically as basophilic and acidophilic foci and acidophilic nodules. Cells in baseophilic foci were large, contained an irregular nucleus and a markedly basophilic cytoplasm with a few to small number of zymogen granules (zymogen-poor cells). By transmission electron microscopy, these cells showed markedly irregular plasma membranes, a well-developed rough endoplasmic reticulum and a few zymogen granules. Cells in acidophilic foci and nodules contained an intensely eosinophilic granular cytoplasm (zymogen-rich cells) and a large oval to round nucleus. By transmission electron microscopy, the cells showed zymogen-rich cytoplasm and irregular lateral plasma membranes. Mitotic activity was completely absent or very rarely observed in normal pancreas or basophilic foci, in contrast to acidophilic foci and nodules in which a mean value of 2.75 +/- 1.27 per 1000 cells was found. Autoradiography confirmed these differences between the proliferative capacity of cells in basophilic foci (1 +/- 1 labeled nuclei per 1000 cells) and acidophilic foci (23.2 +/- 3.15 labeled nuclei per 100 cells). These studies indicate that 4-hydroxyaminoquinoline-1-oxide induces two types of atypical acinar cell foci with different morphologic features and proliferative capacity.