The purpose of this proposed research is to analyze the morphological and functional nature of acinar cell basophilic foci (ABF), induced by the pancreatic carcinogen 4-hydroxyaminoquinoline-1-oxide (4-HAQO), and to study their relationship, if any, to acinar cell acidophilic foci (AAF) and acinar cell nodules (AN), precursor lesions of acinar cell carcinoma.
The specific aims of this proposal are: 1) to investigate the initiation and sequential development of ABF, AAA and AN following a single and multiple injection(s) of 4-HAQO in regenerating and non-regenerating pancreas; 2) to determine whether the development of the various types of nodules can be modulated by soybean trypsin inhibitor; 3) to evaluate functional differences between ABF, AAF and AN by analyzing their proliferative capacity, synthesis and localization of pancreatic enzymes as demonstrated by histo- and immunochemistry, and concanavalin A receptors on their plasma membranes; 4) to develop methods for isolation of cells from ABF, AAF and AN; and 5) to characterize the cells of ABF, AAF and AN biochemically, by measuring mixed function oxidase enzyme activity, synthesis and sulfation of secretory proteins, their response to secretogogues, and quantitation and characterizations of lectins and cholecystokinin receptors.
