[Studies on cell proliferation activities in acute toxic lesions in the liver and pancreas of hamsters treated with N-nitrosobis(2-oxopropyl)amine].

Histopathology and cell proliferation activities in acute toxic lesions in the liver and pancreas of female Syrian hamsters given a S.C. injection of N-nitrosobis(2-oxopropyl)amine (BOP) at a dose of 100 mg/kg, were investigated. Histologically, at one day after administration, hypertrophy and focal necrosis of the hepatocytes were observed, whereas no remarkable changes were seen in the pancreas. At 7 days after administration, when diffuse hypertrophy, vacuolation and necrosis of the hepatocytes, and atypical hyperplasia of the bile duct were seen in the liver, hyperplasia of the pancreatic duct and focal necrosis and vacuolation of the acinar cells were noticed in the pancreas. Immunohistochemistry for both 5-bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) revealed remarkable increases of cell proliferation activities in the target cells for BOP toxicity, especially at 7 days after BOP treatment. Meanwhile, the number per nucleus of silver-stained proteins related to nucleolar organizer regions (AgNOR) was significantly increased in the target cells at both 1 and 7 days after BOP treatment. Thus, in the present study, it was suggested that acute toxic changes in the liver of hamsters treated with BOP precedes those in the pancreas. The speculation that AgNOR may be an indicator recognizing earlier alterations on acute BOP toxicity remains to be examined.