Hepatocarcinogenic effect of vinyl carbamate in the C57Bl/10J strain mouse.
The genotoxic carcinogen vinyl carbamate was dosed to C57Bl/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 hemangiosarcomata. 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.
Wright
J A
JA
ICI Pharmaceuticals, Safety of Medicines Department, Macclesfield, Cheshire, UK.
Marsden
A M
AM
Willets
J M
JM
Orton
T C
TC
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D011519:Proto-Oncogenes / Q000187:drug effects; D013997:Time Factors; D014520:Urethane / Q000031:analogs & derivatives*
D014520:Urethane; C017963:vinyl carbamate