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A Review of the Hepatic Tumors Related to Mixed-Function Oxidase Induction in the Mouse

BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, United Kingdom

Mixed-function oxidase (MFO) induction in the mouse liver results in a rapid and sustained centrilobular hypertrophy associated with a hyperplastic response. In many studies, the long-term sequela of prolonged exposure is an increased incidence of lesions considered to be adenomas. Studies have shown in aged control mice that the burden of adenomas usually consists of lesions with basophilic cytoplasic staining and a uniform population of hepatocyte nuclei. With long-term feeding of MFO inducers, there is an additional burden of lesions diagnosed as adenomas having a different histological appearance with increased eosinophilic cytoplasm and pleomorphic nuclei. The incidence of hepatocarcinomas usually is not modified by the increased incidence of eosinophilic adenomas. Studies into the behavior of the eosinophilic lesions show that the hepatocytes approximate in their behavior to normal and not neoplastic cells. It is suggested that these lesions should not be considered a carcinogenic response to the chemical.

Key Words: Hepatocarcinogens • enzyme induction • hepatic adenoma • hyperplasia

Toxicologic Pathology, Vol. 24, No. 4, 484-492 (1996)
DOI: 10.1177/019262339602400411


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