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Comparative Prevalence, Multiplicity, and Progression of Spontaneous and Vinyl Carbamate-Induced Liver Lesions in Five Strains of Male Mice

Nippon Veterinary and Animal Science University, Tokyo, Japan

Gregg E. Dinse

Biostatistics Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina

Julie F. Foley

Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina

Jerry F. Hardisty

Experimental Pathology Laboratories, Inc, Research Triangle Park, North Carolina

Robert R. Maronpot

Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, maronpot{at}niehs.nih.gov

The overall and age-specific prevalences and multiplicities of spontaneous and chemically induced hepatocellular neoplasia were compared among male B6D2F1, B6C3F1, C3H (C3H/HeNCrl MTV-), B6CF1, and C57BL/6 (C57BL/6NCrl) mice following a single intraperitoneal injection of 0.03 µM 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 µM 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 hepatocarcinogenesi s in all 5 strains.

Key Words: Hepatocarcinogenesis • tumor progression • neonatal mouse model.

References

• Alden CL, Smith PF, Piper CE, Brej L. ( 1996). A critical appraisal of the value of the mouse cancer bioassay in safety assessment. Toxicol Pathol 24: 722—725.[Abstract/Free Full Text]
• Allen J., Langenbach R., Nesnow S., Sasseville K., Leavitt S., Campbell J., Brock K., Sharief Y. (1982). Comparative genotoxicity studies of ethyl carbamate and related chemicals: Further support for vinyl carbamate as a proximate carcinogenic metabolite. Carcinogenesis 3: 1437— 1441.[Abstract/Free Full Text]
• Becker FF ( 1982). Morphological classification of mouse liver tumors based on biological characteristics. Cancer Res 42: 3918—3923.[Abstract/Free Full Text]
• Buchmann A., Bauer-Hofmann R., Mahr J., Drinkwater NR, Luz A., Schwarz M. (1991). Mutational activation of the c-Ha-ras gene in liver tumors of different rodent strains: Correlation with susceptibility to hepatocarcinogenesis. Proc Natl Acad Sci USA 88: 911—915.[Abstract/Free Full Text]
• Butler WH, Newberne PM (1975). Mouse Hepatic Neoplasia. Elsevier Scientific Publishing Company, Amsterdam.
• Counts J., Goodman J. (1993). Comparative analysis of the methylation status of the 5' flanking region of the Ha-ras in B6C3F1, C3H/He and C57BL/6 mouse liver. Cancer Lett 75: 129—136.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Dahl G., Miller E., Miller J. (1980). Comparative carcinogenicities and mutagenicities of vinyl carbamate, ethyl carbamate and ethyl N-hydroxyethylcarbamate. Cancer Res 40: 1194—1203.[Abstract/Free Full Text]
• Dahl G., Miller J., Miller E. (1978). Vinyl carbamate as a promutagen and a more carcinogenic analog of ethyl carbamate. Cancer Res 38: 3793— 3804.[Abstract/Free Full Text]
• Dinse GE, Haseman JK (1986). Logistic regression analysis of incidental-tumor data from animal carcinogenicity experiments. Fundam Appl Toxicol 6: 44—52.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Diwan BA, Rice JM, Ward JM ( 1990). Strain-dependent effects of phenobarbital on liver tumor promotion in inbred mice. Prog Clin Biol Res 331: 69—83.[Medline] [Order article via Infotrieve]
• Dragani TA, Manenti G., Della Porta G. (1991). Quantitative analysis of genetic susceptibility to liver and lung carcinogenesi s in mice. Cancer Res 51:6299—6303.[Abstract/Free Full Text]
• Drinkwater NR, Bennett LM (1991). Genetic control of carcinogenesi s in experimental animals. In: Modification of Tumor Development in Rodents, ITO N, Sugano H (eds). Karger, Basel, pp 1—20.
• Drinkwater NR, Ginsler JJ (1986). Genetic control of hepatocarcinogenesis in C57BL/6J and C3H/HeJ inbred mice. Carcinogenesis 7: 1701— 1707.[Abstract/Free Full Text]
• Fox TR, Schumann AM, Watanable PG, Yano BL, Maher VM, McCormick JJ (1990). Mutational analysis of the H-ras oncogene in spontaneous C57BL/6 x C3H/He mouse liver tumors and tumors induced with genotoxic and nongenotoxic hepatocarcinogens. Cancer Res 50: 4014— 4018.[Abstract/Free Full Text]
• Frith CH, Wiley L. (1982). Spontaneous hepatocellular neoplasms and hepatic hemangiosarcoma s in several strains of mice. Lab Anim Sci 32: 157— 162.[Web of Science][Medline] [Order article via Infotrieve]
• Frome E. (1983). The analysis of rates using Poisson regression models. Biometrics 39: 665—674.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Goldfarb S., Pugh TD, Koen H., He YZ (1983). Preneoplastic and neoplastic progression during hepatocarcinogenesi s in mice injected with diethylnitrosamine in infancy. Environ Health Perspect 50: 149—161.[Web of Science][Medline] [Order article via Infotrieve]
• Grasso P., Hardy J. (1975). Strain differences in natural incidence and response to carcinogenesis. In: Mouse Hepatic Neoplasia, Butler WH, Newberne PM (eds). Elsevier, New York, pp 111—132.
• Guengerich FP, Kim DH (1991). Enzymatic oxidation of ethyl carbamate to vinyl carbamate and its role as an intermediate in the formation of 1,N6-ethenoadenosine. Chem Res Toxicol 4: 413—421.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Hanigan MH, Kemp CJ, Ginsler JJ, Drinkwater NR (1988). Rapid growth of preneoplastic lesions in hepatocarcinogen-sensitiv e C3H/HeJ male mice relative to C57BL/6J male mice. Carcinogenesis 9: 885—890.[Abstract/Free Full Text]
• Hanigan MH, Winkler ML, Drinkwater NR (1993). Induction of three histochemically distinct populations of hepatic foci in C57BL/6J mice. Carcinogenesis 14: 1035—1040.[Abstract/Free Full Text]
• Kakizoe S., Goldfarb S., Pugh TD ( 1989). Focal impairment of growth in hepatocellular neoplasms of C57BL/6 mice: A possible explanation for the strain's resistance to hepatocarcinogenesis. Cancer Res 49: 3985— 3989.[Abstract/Free Full Text]
• Kemp CJ, Drinkwater NR (1989). Genetic variation in liver tumor susceptibility, plasma testosterone levels, and androgen receptor binding in six inbred strains of mice. Cancer Res 49: 5044—5047.[Abstract/Free Full Text]
• Koen H., Pugh TD, Goldfarb S. (1983). Hepatocarcinogenesi s in the mouse. Combined morphologic-stereologi c studies. Am J Pathol 112: 89—100.[Abstract]
• Koen H., Pugh TD, Nychka D., Goldfarb S. (1983). Presence of alphafetoprotein-positive cells in hepatocellular foci and microcarcinomas induced by single injections of diethylnitrosamine in infant mice. Cancer Res 43: 702—708.[Abstract/Free Full Text]
• Lee GH, Bennett LM, Carabeo RA, Drinkwater NR (1995). Identification of hepatocarcinogen-resistanc e genes in DBA/2 mice. Genetics 139: 387—395.[Abstract]
• Malarkey DE, Devereux TR, Dinse GE, Mann PC, Maronpot RR (1995). Hepatocarcinogenicit y of chlordane in B6C3F1 and B6D2F1 male mice: Evidence for regression in B6C3F1 mice and carcinogenesis independent of ras proto-oncogene activation. Carcinogenesis 16: 2617—2625.[Abstract/Free Full Text]
• Maronpot RR,Boorman GA (1996). The contribution of the mouse in hazard identification studies. Toxicol Pathol 24: 726—731.[Abstract/Free Full Text]
• Maronpot RR, Boorman GA, Gaul BW (eds). (1999). Pathology of the Mouse. Cache River Press, Vienna, IL.
• Maronpot RR, Fox T., Malarkey DE, Goldsworthy TL (1995). Mutations in the ras proto-oncogene: Clues to etiology and molecular pathogenesi s of mouse liver tumors. Toxicology 101: 125—156.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Maronpot RR, Haseman JK, Boorman GA, Eustis SE, Rao GN, Huff JE (1987). Liver lesions in B6C3F1 mice: The National Toxicology Program, experience and position. Arch Toxicol Suppl 10: 10—26.[Medline] [Order article via Infotrieve]
• Reynolds SH, Stowers SJ, Maronpot RR, Anderson MW, Aaronson SA (1986). Detection and identification of activated oncogenes in spontaneously occurring benign and malignant hepatocellular tumors of the B6C3F1 mouse. Proc Natl Acad Sci USA 83: 33—37.[Abstract/Free Full Text]
• Reynolds SH, Stowers SJ, Patterson RM, Maronpot RR, Aaronson SA, Anderson MW (1987). Activated oncogene s in B6C3F1 mouse liver tumors: Implications for risk assessment. Science 237: 1309—1316.[Abstract/Free Full Text]
• Ruebner BH, Gershwin ME, French SW, Meierhenry E., Dunn P., Hsieh LS (1984). Mouse hepatic neoplasia: Differences among strains and carcinogens. In: Mouse Liver Neoplasia. Current Perspectives, Popp JA (ed). Hemisphere Publishing Company, New York, pp 115—143.
• Vesselinovitch SD (1987). Certain aspects of hepatocarcinogenesi s in the infant mouse model. Toxicol Pathol 15: 221—228.[Web of Science][Medline] [Order article via Infotrieve]
• Vesselinovitch SD, Mihailovich N. (1983). Kinetics of diethylnitrosamine hepatocarcinogenesi s in the infant mouse. Cancer Res 43: 4253—4259.[Abstract/Free Full Text]
• Vesselinovitch SD, Mihailovich N., Rao KV (1978). Morphology and metastatic nature of induced hepatic nodular lesions in C57BL x C3H F1 mice. Cancer Res 38: 2003—2010.[Abstract/Free Full Text]
• WardJM (1980). Morphology ofhepatocellularneoplasmsinB6C3F1 mice. Cancer Lett 9: 319—325.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Ward JM, Goodman DG, Squire RA, Chu KC, Linhart MS (1979). Neoplastic and nonneoplastic lesions in aging (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice. J Natl Cancer Inst 63: 849—854.[Web of Science][Medline] [Order article via Infotrieve]
• Weghorst CM, Pereira MA, Klaunig JE (1989). Strain differences in hepatic tumor promotion by phenobarbital in diethylnitrosamine- and dimethylnitrosamine-initiated infant male mice. Carcinogenesis 10: 1409— 1412.[Abstract/Free Full Text]
• Wiseman RW, Stowers SJ, Miller EC, Anderson MW, Miller JA (1986). Activating mutations of the c-Ha-ras protooncogen e in chemically induced hepatomas of the male B6C3F1 mouse. Proc Natl Acad Sci USA 83: 5825— 5829.[Abstract/Free Full Text]
• You M., Candrian U., Maronpot RR, Stoner GD, Anderson MW (1989). Activation of the Ki-ras protooncogene in spontaneously occurring and chemically induced lung tumors of the strain A mouse. Proc Natl Acad Sci USA 86: 3070—3074.[Abstract/Free Full Text]

Toxicologic Pathology, Vol. 30, No. 5, 599-605 (2002)
DOI: 10.1080/01926230290105776


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