ORIGIN OF TUBULAR COMPLEXES DEVELOPING DURING INDUCTION OF PANCREATIC ADENOCARCINOMA BY 7,12-DIMETHYLBENZ(A)ANTHRACENE

Abstract

Implantation of 7,12-dimethylbenz(a)anthracene (DMBA) into the pancreas of rats induced adenocarcinoma. Complexes of tubules, which have the appearance of proliferated intralobular ducts, frequently appear during tumor development. These complexes were studied by light microscopy and EM to determine their method of formation. A tubular complex was reconstructed from serial sections to determine its 3-dimensional configuration. Although tubular complexes were thought by others to result from ductal proliferation, the following observations indicate that they originate from zymogen granule-containing cells. There is a continuum of transitional stages between acini and tubules; most tubules decrease in size and are replaced by connective tissue (evidence of regression rather than proliferation), few mitotic figures are seen in tubular complexes; the tubules comprise many cells which have an abundance of rough endoplasmic reticulum, an organelle which is sparse in ducts and the 3-dimensional arrangement of tubules appears identical to the branching, anastomosing arrangement of zymogen granule-containing cells of normal rat pancreas. Control animals in which only sutures were placed in the pancreas showed minimal reaction. Acini become recognized as tubules when loss of zymogen granules accompanies tumor induction by DMBA. Transformation of these cells could be erroneously interpreted as transformation from proliferating ducts.