Characterization of two populations of pancreatic atypical acinar cell foci induced by azaserine in the rat.

Multiple and single intraperitoneal injections of azaserine in male Wistar/Lewis rats induced a 100% incidence of atypical acinar cell foci. The foci were histologically classified into one of two populations, basophilic or acidophilic. The number and size of transections of the foci in tissue sections were determined. By means of known mathematical relationships, focal transectional data were transformed into three-dimensional data (i.e., foci/unit volume, foci/pancreas, mean diameter and volume of foci, and focal volume as percentage of pancreas volume). In general, initiation with azaserine resulted in more acidophilic than basophilic foci. An increase in the azaserine dose from 10 to 30 mg/kg resulted in the initiation of more acidophilic and basophilic foci. Over a 6-month period following initiation, basophilic foci showed a small increase in number and no increase in size. In these same pancreases, acidophilic foci significantly increased in both number and size. A promoter of pancreatic carcinogenesis (20% unsaturated fat diet) enhanced the number and percentage of the pancreas volume occupied by acidophilic foci. This modulator of the postinitiation phase of pancreatic carcinogenesis did not have a significant effect on the basophilic foci. Unlike the basophilic foci, the acidophilic foci show considerable growth potential and appear to be responsive to modulators of carcinogenesis. Further study of this population of carcinogen-induced pancreatic foci is warranted.