Comparative prevalence, multiplicity, and progression of spontaneous and vinyl carbamate-induced liver lesions in five strains of male mice.
The overall and age-specific prevalences and multiplicities of spontaneous and chemically induced hepatocellular neoplasia were compared among male B6D2F1, B6C3F1, C3H (C3H/HeNCr1 MTV-), B6CF1, and C57BL/6 (C57BL/6NCr1) mice following a single intraperitoneal injection of 0.03 microM vinyl carbamate (VC)/g body weight or vehicle alone at 15 days of age. Additional groups of B6C3F1, C3H, and C57BL/6 males received 0.15 microM VC/g body weight at 15 days of age. For male B6D2F1, B6C3F1, C3H, B6CF1, and C57BL/6 mice, the estimated overall prevalences (and multiplicities) of hepatocellular adenomas or carcinomas in vehicle controls were 14.1% (0.19), 12.3% (0.15), 8.2% (0.10), 7.2% (0.09), and 2.4% (0.02), respectively. The analogous estimates in the low-dose group were 59.2% (1.19), 72.9% (4.07), 48.6% (1.99), 22.8% (0.29), and 43.9% (0.82). Analogous estimates for B6C3F1, C3H, and C57BL/6 mice in the high-dose group were 45.3% (4.29), 59.7% (6.63), and 46.8% (1.74), respectively. Age-specific multiplicity estimates suggested a progression from altered hepatocellular foci (AHF) to hepatocellular neoplasms. Further evidence of progression was provided by the temporal occurrence of hepatocellular adenomas before carcinomas, and the apparent origination of carcinomas within adenomas. Pulmonary metastases were observed in many of the mice with hepatocellular carcinomas. These findings confirm previous observations of strain differences in liver neoplasm response, suggest a progressive development from AHF to adenomas, and ultimately to carcinomas, and show sensitivity to VC-induced hepatocarcinogenesis in all 5 strains.
Takahashi
Mimasa
M
Nippon Veterinary and Animal Science University, Tokyo, Japan.
Dinse
Gregg E
GE
Foley
Julie F
JF
Hardisty
Jerry F
JF
Maronpot
Robert R
RR
D018248:Adenoma, Liver Cell / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000453:epidemiology / Q000556:secondary*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D008113:Liver Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011230:Precancerous Conditions / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology*; D013045:Species Specificity; D014520:Urethane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*
D002273:Carcinogens; D014520:Urethane; C017963:vinyl carbamate