Temporal dissociation between cell proliferation and eosinophilic foci development in the exocrine pancreas of rats initiated with 4-hydroxyaminoquinoline 1-oxide and administered soybean trypsin inhibitor.

Male Sprague-Dawley rats received a single i.v. injection of 4-hydroxyaminoquinoline 1-oxide (HAQO) 7 mg/kg body weight or vehicle alone, and starting 7 days thereafter, were then fed basal diet with or without a 5% soybean trypsin inhibitor (SBTI) supplement. Subgroups were sequentially killed after 2, 4, 7, 14, 30, 60 and 100 days on this regimen, in each case 1 h after injection of bromodeoxyuridine (BrdU). In the HAQO/SBTI and SBTI alone groups, 2 days after the SBTI treatment the labeling indices of acinar cells were increased approximately 12- and 11-fold respectively, dropping rapidly thereafter and returning to the control value by day 30. The earliest eosinophilic foci were noted in the HAQO/SBTI group 60 days after HAQO initiation, with the component cells demonstrating markedly increased labeling indices in contrast to the completely normalized levels observed in the surrounding exocrine tissue. On the other hand, eosinophilic foci were scarcely induced in the HAQO or SBTI alone group throughout the experiment. These results thus indicate a clear temporal dissociation between initial proliferation in parenchymal pancreatic tissue caused by SBTI and subsequent development of eosinophilic foci in rats initiated with HAQO.