Atypical acinar cell lesions of the pancreas in mice induced by 4-hydroxyaminoquinoline-1-oxide

The carcinogenic effect of 4-hydroxyaminoquinoline-1-oxide (4-HAQO) on exocrine pancreas of mice after a single intravenous (i.v.) injection was investigated. At a dose of 24 mg/kg body weight, 100% of the mice killed at the end of 40 weeks had developed atypical acinar cell foci (AAF) in the pancreas. Each pancreas contained an average of 18.3±2.7 AAF. Cells in AAF were arranged as acini and their cytoplasm contained eosinophilic zymogen granules. The nuclei were large, round to oval, basally located and contained 1-2 prominent nucleoli. Cells in AAF showed a markedly increased mitotic activity with an index of 4±0.7/1000 cells as compared to a value of 0.25±0.25 in the acinar cell population of control pancreas. Autoradiographic studies showed a labeling index of 23±3 in AAF as compared to only 1.5±0.29 in the pancreatic acinar cells of controls. These findings indicate that 4-HAQO induces pancreatic lesions in mice which are quite similar to the acidophilic foci observed in rat pancreas and may serve as another useful model for studies of pancreatic carcinogenesis.