Ultrastructural analysis of pancreatic carcinogenesis. VI. Early changes in hamster acinar cells induced by N-nitroso-bis(2-hydroxy-propyl)amine

Abstract

Male Syrian golden hamsters were given weekly s.c. injections of 250 mg/kg body weight of N-nitroso-bis(2-hydroxypropyl)amine (BHP) for up to 15 weeks. Electron microscope studies were carried out on early changes in the exocrine pancreas of these hamsters for 2 weeks to 15 weeks. The majority of observed alterations occurred in the acinar cells and included the appearance of "dark" and "light" cells, the former showing nuclear shrinkage and irregularity but maintaining a normal rough endoplasmic reticulum (ER) and zymogen content. The "light" cells exhibited a variety of early fine structural alterations including conformational changes in their rough ER, together with a reduction in zymogen granules, increased autophagic vacuoles and Golgi hypertrophy. Ducts and ductules were relatively unaffected. The observations indicate that the acinar cells were most affected, morphologically, by BHP and are consistent with the view that these cells are the primary target for BHP.

Histogenesis of pancreatic carcinogenesis in the hamster: ultrastructural evidence.

“…Indeed, BHP treatment resulted in very little acinar necrosis, although mitotic cells were observed. However, these rough ER changes are not specific either to BHP or to carcinogens (84).…”

“…Conventional histology revealed little change in the hamster pancreas until after 9 weeks of BHP treatment, when an apparent increase in centroacinar or ductulartype cells becanme evident (79,84). A quantitative study (Moore, unpublished observations) showed, over the first 15 weeks of treatment, a progressive increase in groups containing three or more centroacinar cells and a decline in single cells.…”

“…Intraductal proliferation was rare and neither new islet formation nor early proliferation of intra-insular ductules were observed. However, fine structural changes in acinar cells were evident from the earliest stages and involved at least half of the acinar cell populations after 30 weeks (83,84). The earliest change was the appearance of dark and light cells, differing in the electron density of their ground cytoplasm and nucleoplasm, as shown in Figure 1.…”

Histogenesis of Exocrine Pancreatic Cancer in the Hamster Model

“…There are no other pancreatic cells with this ability, and there is evidence that the ductular cells and centroacinar cells are the most responsive units of the ductal system (2,3,14), based on their enormous potential to display a wide spectrum of phenotypic expression, including various forms of metaplastic change (Figs. [3][4][5][6][7][8]. Formation of glycogen-containing cells ( Fig.…”

“…There are three main points of view with regard to this element of the model. One group of investigators believes pancreatic lesions [at least those induced by Ai N-nitrosobis(2-hydroxypropyl)amine or BHP] derive from acinar cells that undergo ductlike dedifferentiation during carcinogenesis (4,5). Another group has the ,, distinct view that all induced lesions in hamsters derive i from ductal and ductular cells (2,3,6,7).…”