Hepatocarcinogenic Effect of Vinyl Carbamate in the C57B1/10J Strain Mouse

Author:

Wright Jayne A.1,Marsden Alan M.1,Willets Jonathan M.1,Orton Telly C.1

Affiliation:

1. ICI Pharmaceuticals, Safety of Medicines Department, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK

Abstract

The genotoxic carcinogen vinyl carbamate was dosed to C57B1/10J strain mice for 35 weeks, and the study terminated after week 59. A main study group of 55 males and 50 females was dosed 6 mg/kg vinyl carbamate once weekly by intraperitoneal injection, whilst a reference group of 10 animals/sex were kept undosed. From week 39 onwards there was a high incidence of mortality, which was often associated with acute internal abdominal hemorrhage. Mice of both sexes killed from 34 weeks onwards frequently showed macroscopic evidence of blood-filled, cyst-like structures in the liver. Upon histopathological examination widespread peliosis hepatis was observed with frequent progression to hemangiomata and hemangiosarco-. mata. Trabecular hepatocellular carcinomata were also apparent, often within the same liver sections and invariably associated with peliosis hepatis. As a consequence of its tumor burden, the liver often showed hepatocyte atrophy, fibrosis, and coagulation necrosis. A small number of livers revealed hepatocellular adenomata and altered hepatocyte foci.

Publisher

SAGE Publications

Subject

Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine

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