An in vitro model of chemical carcinogenesis of human pancreas, developed in this laboratory, allows cloning and examination of exocrine cells at various carcinogenic steps induced by methyinitrosourea (MNU). In this model morphological (hyperplasia, atypia, and anaplasia) and biological (""""""""growth enhancement"""""""", increases in the number of cell generations before senescence, """"""""immortality"""""""" and """"""""tumorigenicity"""""""") steps have been described. For the identification of new steps and the better characterization of the already described ones more than 60 monoclonal antibodies to normal and MNU-treated human pancreas were raised. A few of these have been partially characterized and allow the detection of acinar, ductal, centroacinar, islet cells and a subpopulation of cells, """"""""progenitor cells"""""""", which appears two weeks after MNU-treatment. The remaining antibodies were selected based on their affinities for membrane, and cytoplasm and/or nuclei of the tissue used as immunogens, and their lack of affinity for HLA and blood group antigens as tested by sections of spleens from pancreatic donors. It is proposed to use normal and MNU-treated human pancreas as well as clonal growths and cell lines derived from human pancreas explants exposed to various doses of MNU to establish cell- and/or stage-specificity for these reagents. It is further proposed to use a selective number of these antibodies to focus on the early stages in carcinogenesis: a) from initiated to progenitor cell and b) from clonal growths to immortality.
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| Parsa, I; Longnecker, D S; Scarpelli, D G et al. (1985) Ductal metaplasia of human exocrine pancreas and its association with carcinoma. Cancer Res 45:1285-90 |
