Experimental mouse models for hepatocellular carcinoma research

International Journal of Experimental Pathology

Volumn 90, Issue 4, 2009, Pages 367-386

  Heindryckx, Femke ^a,b   Colle, Isabelle ^a   Van Vlierberghe, Hans ^a  

^a GHENT UNIVERSITY HOSPITAL   (Belgium)

^b Department of Gastroenterology and Hepatology ^*  (Belgium)

Author keywords

Hepatocellular carcinoma; Hepatology; Hollow fibre assay; Mouse models; Transgenic mice; Xenograft

Indexed keywords

5 CYCLOPROPYL 2 (4 FLUOROPHENYL) 6 [N (2 HYDROXYETHYL)METHANESULFONAMIDO] N METHYLBENZOFURAN 3 CARBOXAMIDE; AFLATOXIN B1; ALPHA 1 ANTITRYPSIN; BETA CATENIN; CARBON TETRACHLORIDE; DIETHYLNITROSAMINE; FIBROBLAST GROWTH FACTOR; FIBROBLAST GROWTH FACTOR 19; GLYCINE METHYLTRANSFERASE; GROWTH FACTOR; PEROXISOME PROLIFERATOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PLATELET DERIVED GROWTH FACTOR; RAS PROTEIN; THIOACETAMIDE; TRANSCRIPTION FACTOR E2F1; TRANSCRIPTION FACTOR ELF 1; TRANSFORMING GROWTH FACTOR ALPHA; TRANSFORMING GROWTH FACTOR BETA1; TUMOR PROMOTER; UNCLASSIFIED DRUG; VIRUS T ANTIGEN;

CANCER CELL CULTURE; CANCER GROWTH; CANCER MODEL; CANCER RESEARCH; CANCER TRANSPLANTATION; CHEMICALLY INDUCED DISORDER; DIET RESTRICTION; DNA MODIFICATION; DRUG CARCINOGENICITY; DRUG SCREENING; GENE EXPRESSION; GENE MUTATION; GENOTOXICITY; HEPATOMA CELL; HOLLOW FIBER; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LUNG FIBROSIS; LUNG INJURY; MOUSE; NONHUMAN; ONCOGENE C MYC; PRIORITY JOURNAL; REVIEW; SIMIAN VIRUS 40; TRANSGENIC MOUSE; TUMOR PROMOTION; TUMOR XENOGRAFT; VIRUS ONCOGENE;

ANIMALS; CARCINOGENS; CARCINOMA, HEPATOCELLULAR; DISEASE MODELS, ANIMAL; HUMANS; LIVER NEOPLASMS; LIVER NEOPLASMS, EXPERIMENTAL; MICE; MICE, TRANSGENIC; MODELS, ANIMAL; RESEARCH; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 68849118378     PISSN: 09599673     EISSN: 13652613     Source Type: Journal    
DOI: 10.1111/j.1365-2613.2009.00656.x     Document Type: Review

References (174)

1. Araki K., Miyazaki J., Hino O. et al. (1989) Expression and replication of hepatitis B virus genome in transgenic mice. Proc. Natl Acad. Sci. USA 86, 207 211.
2. Araki K., Hino O., Miyazaki J., Yamamura K. (1991) Development of 2 types of hepatocellular-carcinoma in transgenic mice carrying the Sv40 large T-antigen gene. Carcinogenesis 12, 2059 2062.
3. Autrup H. Wakhisi J. (1988) Detection of exposure to aflatoxin in an African population. IARC Sci. Publ., 8, 63 66.
4. Avantaggiati M.L., Natoli G., Balsano C. et al. (1993) The hepatitis B virus (HBV) pX transactivates the c-fos promoter through multiple cis-acting elements. Oncogene 8, 1567 1574.
5. Avasarala S., Yang L., Sun Y. et al. (2006) A temporal study on the histopathological, biochemical and molecular responses of CCl(4)-induced hepatotoxicity in Cyp2e1-null mice. Toxicology 228, 310 322.
6. Aydinlik H., Nguyen T.D., Moennikes O., Buchmann A., Schwarz M. (2001) Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of beta-catenin-mutated mouse liver tumors. Oncogene 20, 7812 7816.
7. Babinet C., Farza H., Morello D., Hadchouel M., Pourcel C. (1985) Specific expression of hepatitis-B surface-antigen (Hbsag) in transgenic mice. Science 230, 1160 1163.
8. Baek H.J., Lim S.C., Kitisin K. et al. (2008) Hepatocellular cancer arises from loss of transforming growth factor beta signaling adaptor protein embryonic liver fodrin through abnormal angiogenesis. Hepatology 48, 1128 1137.
9. Binato M., Kruel Schmidt M., Silveira Volkweis B., Behrend Silva Ribeiro G., Isabel Edelweiss M., Ricachenevsky Gurski R. (2008) Mouse model of diethylnitrosamine-induced gastric cancer. J. Surg. Res. 148 (2 152 157.
10. Bird A.P. Wolffe A.P. (1999) Methylation-induced repression - belts, braces, and chromatin. Cell 99, 451 454.
11. Bonner J.C. (2004) Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev. 15, 255 273.
12. Borkham-Kamphorst E., van Roeyen C.R.C., Ostendorf T., Floege J., Gressner A.M., Weiskirchen R. (2007) Pro-fibrogenic potential of PDGF-D in liver fibrosis. J. Hepatol. 46, 1064 1074.
13. Borlak J., Meier T., Halter R., Spanel R., Spanel-Borowski K. (2005) Epidermal growth factor-induced hepatocellular carcinoma: gene expression profiles in precursor lesions, early stage and solitary tumours. Oncogene 24, 1809 1819.
14. Brembeck F.H., Rosario M., Birchmeier W. (2006) Balancing cell adhesion and Wnt signaling, the key role of beta-catenin. Curr. Opin. Genet. Dev. 16, 51 59.
15. Buchmann A., Bauerhofmann R., Mahr J., Drinkwater N.R., 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.
16. Burk R.D., Deloia J.A., Elawady M.K., Gearhart J.D. (1988) Tissue preferential expression of the hepatitis-B virus (Hbv) surface-antigen gene in 2 lines of Hbv transgenic mice. J. Virol. 62, 649 654.
17. Calfee-Mason K.G., Lee E.Y., Spear B.T., Glauert H.P. (2008) Role of the p50 subunit of NF-kappa B in vitamin E-induced changes in mice treated with the peroxisome proliferator, ciprofibrate. Food Chem. Toxicol. 46, 2062 2073.
18. Calvisi D.F., Ladu S., Gorden A. et al. (2006) Ubiquitous activation of Ras and Jak/Stat pathways in human HCC. Gastroenterology 130, 1117 1128.
19. Campbell J.S., Hughes S.D., Gilbertson D.G. et al. (2005) Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma. Proc. Natl Acad. Sci. USA 102, 3389 3394.
20. Chang M.L., Yeh C.T., Chen J.C. et al. (2008) Altered expression patterns of lipid metabolism genes in an animal model of HCV core-related, nonobese, modest hepatic steatosis. BMC Genomics 9, 109.
21. Chen B., Liu L., Castonguay A., Maronpot R.R., Anderson M.W., You M. (1993) Dose-dependent Ras mutation spectra in N-nitrosodiethylamine induced mouse-liver tumors and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone induced mouse lung-tumors. Carcinogenesis 14, 1603 1608.
22. Cheung C., Akiyama T.E., Ward J.M. et al. (2004) Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha. Cancer Res. 64, 3849 3854.
23. Chisari F.V., Pinkert C.A., Milich D.R. et al. (1985) A transgenic mouse model of the chronic hepatitis-B surface-antigen carrier state. Science 230, 1157 1160.
24. Confer D.B. Stenger R.J. (1966) Nodules in livers of C3h mice after long-term carbon tetrachloride administration - a Light and Electron Microscopic Study. Cancer Res. 26, 834 843.
25. Conner E.A., Lemmer E.R., Sanchez A., Factor V.M., Thorgeirsson S.S. (2003) E2F1 blocks and c-Myc accelerates hepatic ploidy in transgenic mouse models. Biochem. Biophys. Res. Commun. 302, 114 120.
26. Counts J.L. Goodman J.I. (1995) Hypomethylation of DNA: a nongenotoxic mechanism involved in tumor promotion. Toxicol. Lett. 82-83, 663 672.
27. Cullen J.M., Sandgren E.P., Brinster R.L., Maronpot R.R. (1993) Histologic characterization of hepatic carcinogenesis in transgenic mice expressing SV40 T-antigens. Vet. Pathol. 30, 111 118.
28. Cullen J.M., Lindsey-Pegram D., Cote P.J. (2008) Serologic survey of woodchuck hepatitis virus in North Carolina woodchucks (Marmota monax). J. Zoo Wildl. Med. 39, 263 265.
29. Czochra P., Klopcic B., Meyer E. et al. (2006) Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice. J. Hepatol. 45, 419 428.
30. Dang C.V. Lewis B.C. (1997) Role of oncogenic transcription factor c-Myc in cell cycle regulation, apoptosis and metabolism. J. Biomed. Sci. 4, 269 278.
31. Decker S., Hollingshead M., Bonomi C.A., Carter J.P., Sausville E.A. (2004) The hollow fibre model in cancer drug screening: the NCI experience. Eur. J. Cancer 40, 821 826.
32. Deng L., Nagano-Fujii M., Tanaka M. et al. (2006) NS3 protein of Hepatitis C virus associates with the tumour suppressor p53 and inhibits its function in an NS3 sequence-dependent manner. J. Gen. Virol. 87, 1703 1713.
33. Devereux T.R., Anna C.H., Foley J.F., White C.M., Sills R.C., Barrett J.C. (1999) Mutation of beta-catenin is an early event in chemically induced mouse hepatocellular carcinogenesis. Oncogene 18, 4726 4733.
34. Diwan B.A., Rice J.M., Ward J.M., Ohshima M., Lynch P.H. (1984) Inhibition by phenobarbital and lack of effect of amobarbital on the development of liver tumors induced by N-nitrosodiethylamine in juvenile B6C3F1 mice. Cancer Lett. 23, 223 234.
35. Diwan B.A., Rice J.M., Ohshima M., Ward J.M. (1986) Interstrain differences in susceptibility to liver carcinogenesis initiated by N-nitrosodiethylamine and its promotion by phenobarbital in C57BL/6NCr, C3H/HeNCrMTV- and DBA/2NCr mice. Carcinogenesis 7, 215 220.
36. Dubois N., Bennoun M., Allemand I. et al. (1991) Time-course development of differentiated hepatocarcinoma and lung metastasis in transgenic mice. J. Hepatol. 13, 227 239.
37. ElRefaie A., Savage K., Bhattacharya S. et al. (1996) HCV-associated hepatocellular carcinoma without cirrhosis. J. Hepatol. 24, 277 285. (Pubitemid 26104883)
38. Farazi P.A., Glickman J., Horner J., Depinho R.A. (2006) Cooperative interactions of p53 mutation, telomere dysfunction, and chronic liver damage in hepatocellular carcinoma progression. Cancer Res. 66, 4766 4773.
39. Farber E. (1984) The multistep nature of cancer development. Cancer Res. 44, 4217 4223.
40. Farber E., Solt D., Cameron R., Laishes B., Ogawa K., Medline A. (1977) Newer insights into pathogenesis of liver cancer. Am. J. Pathol. 89, 477 482.
41. Feng X.Y., Zhang H.Q., Liu H.Z. et al. (2007) Cancerogenic effect of different fragments of the hepatitis C virus core protein. Eur. J. Cancer Prev. 16, 304 311.
42. Finnberg N., Stenius U., Hogberg J. (2004) Heterozygous p53-deficient (+/-) mice develop fewer p53-negative preneoplastic focal liver lesions in response to treatment with diethylnitrosamine than do wild-type (+/+) mice. Cancer Lett. 207, 149 155.
43. Frese K.K. Tuveson D.A. (2007) Maximizing mouse cancer models. Nat. Rev. Cancer 7, 645 658.
44. Frey S., Buchmann A., Bursch W., Schulte-Hermann R., Schwarz M. (2000) Suppression of apoptosis in C3H mouse liver tumors by activated Ha-ras oncogene. Carcinogenesis 21, 161 166.
45. Gallagher E.P., Wienkers L.C., Stapleton P.L., Kunze K.L., Eaton D.L. (1994) Role of human microsomal and human complementary DNA-expressed cytochromes P4501A2 and P4503A4 in the bioactivation of aflatoxin B1. Cancer Res. 54, 101 108.
46. Geller S.A., Nichols W.S., Kim S. et al. (1994) Hepatocarcinogenesis is the sequel to hepatitis in Z#2 alpha 1-antitrypsin transgenic mice: histopathological and DNA ploidy studies. Hepatology 19, 389 397.
47. Gerber M.A. (1993) Relation of hepatitis-C virus to hepatocellular- carcinoma. J. Hepatol. 17, S108 S111.
48. Ghebranious N. Sell S. (1998) The mouse equivalent of the human p53ser249 mutation p53ser246 enhances aflatoxin hepatocarcinogenesis in hepatitis B surface antigen transgenic and p53 heterozygous null mice. Hepatology 27, 967 973.
49. Goldsworthy T.L. Fransson-Steen R. (2002) Quantitation of the cancer process in C57BL/6J, B6C3F1 and C3H/HeJ mice. Toxicol. Pathol. 30, 97 105.
50. Gray R., Peto R., Brantom P., Grasso P. (1991) Chronic nitrosamine ingestion in 1040 rodents: the effect of the choice of nitrosamine, the species studied, and the age of starting exposure. Cancer Res. 51, 6470 6491.
51. Gudima S., He Y.P., Chai N. et al. (2008) Primary human hepatocytes are susceptible to infection by hepatitis delta virus assembled with envelope proteins of woodchuck hepatitis virus. J. Virol. 82, 7276 7283.
52. Hacker H.J., Mtiro H., Bannasch P., Vesselinovitch S.D. (1991) Histochemical profile of mouse hepatocellular adenomas and carcinomas induced by a single dose of diethylnitrosamine. Cancer Res. 51, 1952 1958.
53. Harada N., Miyoshi H., Murai N. et al. (2002) Lack of tumorigenesis in the mouse liver after adenovirus-mediated expression of a dominant stable mutant of beta-catenin. Cancer Res. 62, 1971 1977.
54. Harada N., Oshima H., Katoh M., Tamai Y., Oshima M., Taketo M.M. (2004) Hepatocarcinogenesis in mice with beta-catenin and Ha-Ras gene mutations. Cancer Res. 64, 48 54.
55. Hasmall S.C., James N.H., Macdonald N., Gonzalez F.J., Peters J.M., Roberts R.A. (2000) Suppression of mouse hepatocyte apoptosis by peroxisome proliferators: role of PPAR alpha and TNF alpha. Mutat. Res. Fundam. Mol. Mech. Mutagen. 448, 193 200.
56. Hays T., Rusyn I., Burns A.M. et al. (2005) Role of peroxisome proliferator-activated receptor-alpha (PPARalpha) in bezafibrate-induced hepatocarcinogenesis and cholestasis. Carcinogenesis 26, 219 227.
57. Hollingshead M.G., Alley M.C., Camalier R.F. et al. (1995) In vivo cultivation of tumor cells in hollow fibers. Life Sci. 57, 131 141.
58. Horie Y., Suzuki A., Kataoka E. et al. (2004) Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J. Clin. Invest. 113, 1774 1783.
59. Hsu H.C., Jeng Y.M., Mao T.L., Chu J.S., Lai P.L., Peng S.Y. (2000) Beta-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis. Am. J. Pathol. 157, 763 770.
60. Hu K.Q., Yu C.H., Vierling J.M. (1992) Up-regulation of intercellular adhesion molecule 1 transcription by hepatitis B virus X protein. Proc. Natl Acad. Sci. USA 89, 11441 11445.
61. Huynh H., Soo K.C., Chow P.K.H., Panasci L., Tran E. (2006) Xenografts of human hepatocellular carcinoma: a useful model for testing drugs. Clin. Cancer Res. 12, 4306 4314.
62. Iida M., Anna C.H., Hartis J. et al. (2003) Changes in global gene and protein expression during early mouse liver carcinogenesis induced by non-genotoxic model carcinogens oxazepam and Wyeth-14,643. Carcinogenesis 24, 757 770.
63. Imaoka S., Osada M., Minamiyama Y. et al. (2004) Role of phenobarbital-inducible cytochrome P450s as a source of active oxygen species in DNA-oxidation. Cancer Lett. 203, 117 125.
64. Jhappan C., Stahle C., Harkins R.N., Fausto N., Smith G.H., Merlino G.T. (1990) TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell 61, 1137 1146.
65. Kamegaya Y., Hiasa Y., Zukerberg L. et al. (2005) Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis. Hepatology 41, 660 667.
66. Kanamura S., Kanai K., Watanabe J. (1990) Fine-structure and function of hepatocytes during development. J. Electron Microsc. Tech. 14, 92 105.
67. Kawamura T., Furusaka A., Koziel M.J. et al. (1997) Transgenic expression of hepatitis C virus structural proteins in the mouse. Hepatology 25, 1014 1021.
68. Kawanishi S., Hiraku Y., Murata M., Oikawa S. (2002) The role of metals in site-specific DNA damage with reference to carcinogenesis. Free Radic. Biol. Med. 32, 822 832.
69. Kelland L.R. (2004) Of mice and men: values and liabilities of the athymic nude mouse model in anticancer drug development. Eur. J. Cancer 40, 827 836.
70. Keller B.J., Yamanaka H., Liang D., Thurman R.G. (1990) Hepatotoxicity due to clofibrate is oxygen-dependent in the perfused-rat-liver. Toxicol. Appl. Pharmacol. 104, 259 266.
71. Klaunig J.E., Pereira M.A., Ruch R.J., Weghorst C.M. (1988) Dose-response relationship of diethylnitrosamine-initiated tumors in neonatal balb/c mice: effect of phenobarbital promotion. Toxicol. Pathol. 16, 381 385.
72. Klinman N.R. Erslev A.J. (1963) Cellular response to partial hepatectomy. Proc. Soc. Exp. Biol. Med. 112, 338 340.
73. Knight B., Yeoh G.C., Husk K.L. et al. (2000) Impaired preneoplastic changes and liver tumor formation in tumor necrosis factor receptor type 1 knockout mice. J. Exp. Med. 192, 1809 1818.
74. Koike K., Moriya K., Iino S. et al. (1994) High-level expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic mice. Hepatology 19, 810 819. (Pubitemid 24109339)
75. Kolaja K.L. Klaunig J.E. (1997) Vitamin E modulation of hepatic focal lesion growth in mice. Toxicol. Appl. Pharmacol. 143, 380 387.
76. Koo J.S., Seong J.K., Park C. et al. (2005) Large liver cell dysplasia in hepatitis B virus X transgenic mouse liver and human chronic hepatitis B virus-infected liver. Intervirology 48, 16 22.
77. Kornek M., Raskopf E., Tolba R. et al. (2008) Accelerated orthotopic hepatocellular carcinomas growth is linked to increased expression of pro-angiogenic and prometastatic factors in murine liver fibrosis. Liver Int. 28, 509 518.
78. Lakhtakia R., Kumar V., Reddi H., Mathur M., Dattagupta S., Panda S.K. (2003) Hepatocellular carcinoma in a hepatitis B 'x' transgenic mouse model: a sequential pathological evaluation. J. Gastroenterol. Hepatol. 18, 80 91. (Pubitemid 36062592)
79. Lan K.H., Sheu M.L., Hwang S.J. et al. (2002) HCVNS5A interacts with p53 and inhibits p53-mediated apoptosis. Oncogene 21, 4801 4811.
80. Laurent-Puig P. Zucman-Rossi J. (2006) Genetics of hepatocellular tumors. Oncogene 25, 3778 3786.
81. Lechuga C.G., Hernandez-Nazara Z.H., Dominguez Rosales J.A., Morris E.R., Rincon A.R., Rivas-Estilla A.M., Esteban-Gamboa A. Rojkind M. (2004) TGF-beta1 modulates matrix metalloproteinase-13 expression in hepatic stellate cells by complex mechanisms involving p38MAPK, PI3-kinase, AKT, and p70S6k. Am J Physiol Gastrointest Liver Physiol 287, G974 987.
82. Ledda-Columbano G.M., Perra A., Concas D. et al. (2003) Different effects of the liver mitogens triiodo-thyronine and ciprofibrate on the development of rat hepatocellular carcinoma. Toxicol. Pathol. 31, 113 120.
83. Lee T.H., Finegold M.J., Shen R.F., DeMayo J.L., Woo S.L., Butel J.S. (1990) Hepatitis B virus transactivator X protein is not tumorigenic in transgenic mice. J. Virol. 64, 5939 5947.
84. Lee G.H., Ooasa T., Osanai M. (1998) Mechanism of the paradoxical, inhibitory effect of phenobarbital on hepatocarcinogenesis initiated in infant B6C3F1 mice with diethylnitrosamine. Cancer Res. 58, 1665 1669.
85. Lee J.S., Chu I.S., Mikaelyan A. et al. (2004) Application of comparative functional genomics to identify best-fit mouse models to study human cancer. Nat. Genet. 36, 1306 1311.
86. Lefevre P.A., Tinwell H., Galloway S.M. et al. (1994) Evaluation of the genetic toxicity of the peroxisome proliferator and carcinogen methyl clofenapate, including assays using muta(Tm)mouse and Big Blue(Tm) transgenic mice. Hum. Exp. Toxicol. 13, 764 775.
87. Lerat H., Honda M., Beard M.R. et al. (2002) Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology 122, 352 365.
88. Li X.L., Liu J.Y., Lu R. et al. (2008) Evaluation of the therapeutic efficacy of tripeptide tyroserleutide (YSL) for human hepatocarcinoma by in vivo hollow fiber assay. Invest. New Drugs 26 (6 525 529.
89. de Lima V.M., Oliveira C.P., Alves V.A. et al. (2008) A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma. J. Hepatol. 49, 1055 1061.
90. Liquori G.E., Calamita G., Cascella D., Mastrodonato M., Portincasa P., Ferri D. (2009) An innovative methodology for the automated morphometric and quantitative estimation of liver steatosis. Histol. Histopathol. 24, 49 60.
91. Liu S.P., Li Y.S., Chen Y.J. et al. (2007) Glycine N-methyltransferase-/- mice develop chronic hepatitis and glycogen storage disease in the liver. Hepatology 46, 1413 1425.
92. Loeppen S., Schneider D., Gaunitz F. et al. (2002) Overexpression of glutamine synthetase is associated with beta-catenin-mutations in mouse liver tumors during promotion of hepatocarcinogenesis by phenobarbital. Cancer Res. 62, 5685 5688.
93. Lou D.Q., Molina T., Bennoun M. et al. (2005) Conditional hepatocarcinogenesis in mice expressing SV 40 early sequences. Cancer Lett. 229, 107 114.
94. Lu M.J., Yao X., Xu Y. et al. (2008) Combination of an antiviral drug and immunomodulation against hepadnaviral infection in the woodchuck model. J. Virol. 82, 2598 2603.
95. Ma X.F., Stoffregen D.A., Wheelock G.D., Rininger J.A., Babish J.G. (1997) Discordant hepatic expression of the cell division control enzyme p34(cdc2) kinase, proliferating cell nuclear antigen, p53 tumor suppressor protein, and p21(Waf1) cyclin-dependent kinase inhibitory protein after WY14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid) dosing to rats. Mol. Pharmacol. 51, 69 78.
96. Mao T.L., Chu J.S., Jeng Y.M., Lai P.L., Hsu H.C. (2001) Expression of mutant nuclear beta-catenin correlates with non-invasive hepatocellular carcinoma, absence of portal vein spread, and good prognosis. J. Pathol. 193, 95 101.
97. Martinez-Chantar M.L., Vazquez-Chantada M., Ariz U. et al. (2008) Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice. Hepatology 47, 1191 1199.
98. Mato J.M. Lu S.C. (2007) Role of S-adenosyl-L-methionine in liver health and injury. Hepatology 45, 1306 1312.
99. Matsuo M., Sakurai H., Saiki I. (2003) ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, shows activity using a hepatocellular carcinoma model. Mol. Cancer Ther. 2, 557 561.
100. McGlynn K.A., Hunter K., LeVoyer T. et al. (2003) Susceptibility to aflatoxin B-1-related primary hepatocellular carcinoma in mice and humans. Cancer Res. 63, 4594 4601.
101. Merle P., Kim M., Herrmann M. et al. (2005) Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma. J. Hepatol. 43, 854 862. (Pubitemid 41414512)
102. Morimura K., Cheung C., Ward J.M., Reddy J.K., Gonzalez F.J. (2006) Differential susceptibility of mice humanized for peroxisome proliferator-activated receptor alpha to Wy-14,643-induced liver tumorigenesis. Carcinogenesis 27, 1074 1080.
103. Moriya K., Fujie H., Shintani Y. et al. (1998) The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat. Med. 4, 1065 1067.
104. Motola-Kuba D., Zamora-Valdes D., Uribe M., Mendez-Sanchez N. (2006) Hepatocellular carcinoma. An overview. Ann. Hepatol. 5, 16 24.
105. Murakami H., Sanderson N.D., Nagy P., Marino P.A., Merlino G., Thorgeirsson S.S. (1993) Transgenic mouse model for synergistic effects of nuclear oncogenes and growth factors in tumorigenesis: interaction of c-myc and transforming growth factor alpha in hepatic oncogenesis. Cancer Res. 53, 1719 1723.
106. Naas T., Ghorbani M., Alvarez-Maya I. et al. (2005) Characterization of liver histopathology in a transgenic mouse model expressing genotype 1a hepatitis C virus core and envelope proteins 1 and 2. J. Gen. Virol. 86, 2185 2196.
107. Nagini S. Nagarajan B. (1988) Hypolipidemic drug clofibrate promotes hepatic tumor. Biochem. Int. 17, 605 610. (Pubitemid 18267761)
108. Nakatani T., Roy G., Fujimoto N., Asahara T., Ito A. (2001) Sex hormone dependency of diethylnitrosamine-induced liver tumors in mice and chemoprevention by leuprorelin. Jpn. J. Cancer Res. 92, 249 256.
109. Nicholes K., Guillet S., Tomlinson E. et al. (2002) A mouse model of hepatocellular carcinoma - Ectopic expression of fibroblast growth factor 19 in skeletal muscle of transgenic mice. Am. J. Pathol. 160, 2295 2307.
110. Nilsson J.A. Cleveland J.L. (2003) Myc pathways provoking cell suicide and cancer. Oncogene 22, 9007 9021.
111. Nishimura J., Nishimura J., Dewa Y. et al. (2007) Mechanistic study on fenofibrate-induced hepatocarcinogenesis in a 2-stage hepatocarcinogenesis model of rats: Involvement of oxidative stress. Toxicol. Lett. 172, S173 S173.
112. Ohgaki H., Sanderson N.D., Ton P., Thorgeirsson S.S. (1996) Molecular analyses of liver tumors in c-myc transgenic mice and c-myc and TGF-alpha double transgenic mice. Cancer Lett. 106, 43 49.
113. Palacios R.S., Roderfeld M., Hemmann S. et al. (2008) Activation of hepatic stellate cells is associated with cytokine expression in thioacetamide-induced hepatic fibrosis in mice. Lab. Invest. 88, 1192 1203.
114. Park T.J., Kim J.Y., Oh S.P. et al. (2008) TIS21 negatively regulates hepatocarcinogenesis by disruption of cyclin B1-Forkhead box M1 regulation loop. Hepatology 47, 1533 1543.
115. Parkin D.M., Bray F., Ferlay J., Pisani P. (2001) Estimating the world cancer burden: Globocan 2000. Int. J. Cancer 94, 153 156. (Pubitemid 32911406)
116. Pegg A.E. (1990) Mammalian O6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents. Cancer Res. 50, 6119 6129.
117. Peters J.M., Cattley R.C., Gonzalez F.J. (1997) Role of PPAR alpha in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643. Carcinogenesis 18, 2029 2033.
118. Phillips R.M., Pearce J., Double J.A. (1998) Temporal characterisation of blood vessel development to hollow fibres: Implications for drug delivery and drug evaluation. Ann. Oncol. 9, 72 72.
119. Pitot H.C. Dragan Y.P. (1991) Facts and theories concerning the mechanisms of carcinogenesis. FASEB J. 5, 2280 2286.
120. Qi W., Chen X.M., Holian J. et al. (2006) Transforming growth factor-beta(1) differentially mediates fibronectin and inflammatory cytokine expression in kidney tubular cells. Am. J. Physiol. Renal. Physiol. 291, F1070 F1077.
121. Qi Y.T., Chen X., Chan C.Y. et al. (2008) Two-dimensional differential gel electrophoresis/analysis of diethylnitrosamine induced rat hepatocellular carcinoma. Int. J. Cancer 122, 2682 2688.
122. Ramsdell H.S., Parkinson A., Eddy A.C., Eaton D.L. (1991) Bioactivation of aflatoxin B1 by human liver microsomes: role of cytochrome P450 IIIA enzymes. Toxicol. Appl. Pharmacol. 108, 436 447.
123. Rao M.S. Reddy J.K. (1996) Hepatocarcinogenesis of peroxisome proliferators. Peroxisomes: Biol. Role Toxicol. Dis. 804, 573 587.
124. Rao K.V. Vesselinovitch S.D. (1973) Age- and sex-associated diethylnitrosamine dealkylation activity of the mouse liver and hepatocarcinogenesis. Cancer Res. 33, 1625 1627.
125. Reddy J.K., Rao S., Moody D.E. (1976) Hepatocellular carcinomas in acatalasemic mice treated with nafenopin, a hypolipidemic peroxisome proliferator. Cancer Res. 36, 1211 1217.
126. Roberts R.A., Soames A.R., Gill J.H., James N.H., Wheeldon E.B. (1995) Nongenotoxic hepatocarcinogens stimulate DNA-synthesis and their withdrawal induces apoptosis, but in different hepatocyte populations. Carcinogenesis 16, 1693 1698.
127. Sanderson N., Factor V., Nagy P. et al. (1995) Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions. Proc. Natl Acad. Sci. USA 92, 2572 2576.
128. Schnur J., Olah J., Szepesi A., Nagy P., Thorgeirsson S.S. (2004) Thioacetamide-induced hepatic fibrosis in transforming growth factor beta-1 transgenic mice. Eur. J. Gastroenterol. Hepatol. 16, 127 133.
129. Schwarz M., Wanke I., Wulbrand U., Moennikes O., Buchmann A. (2003) Role of connexin32 and beta-catenin in tumor promotion in mouse liver. Toxicol. Pathol. 31, 99 102.
130. Sell S., Hunt J.M., Dunsford H.A., Chisari F.V. (1991) Synergy between hepatitis-B virus expression and chemical hepatocarcinogens in transgenic mice. Cancer Res. 51, 1278 1285.
131. Sepulveda A.R., Finegold M.J., Smith B. et al. (1989) Development of a transgenic mouse system for the analysis of stages in liver carcinogenesis using tissue-specific expression of SV40 large T-antigen controlled by regulatory elements of the human alpha-1-antitrypsin gene. Cancer Res. 49, 6108 6117.
132. Shao D.M., Wang Q.H., Chen C. et al. (1999) N- acetylglucosaminyltransferase V activity in metastatic models of human hepatocellular carcinoma in nude mice. J. Exp. Clin. Cancer Res. 18, 331 335.
133. Sheweita S.A., El-Gabar M.A., Bastawy M. (2001) Carbon tetrachloride changes the activity of cytochrome P450 system in the liver of male rats: role of antioxidants. Toxicology 169, 83 92. (Pubitemid 33082115)
134. Shiota G., Harada K., Ishida M. et al. (1999) Inhibition of hepatocellular carcinoma by glycyrrhizin in diethylnitrosamine-treated mice. Carcinogenesis 20, 59 63.
135. Shnyder S.D., Cooper P.A., Scally A.J., Bibby M.C. (2006) Reducing the cost of screening novel agents using the hollow fibre assay. Anticancer Res. 26, 2049 2052.
136. Stahl S., Ittrich C., Marx-Stoelting P. et al. (2005) Genotype-phenotype relationships in hepatocellular tumors from mice and man. Hepatology 42, 353 361.
137. Suggitt M., Cooper P.A., Shnyder S.D., Bibby M.C. (2006) The hollow fibre model - facilitating anti-cancer pre-clinical pharmacodynamics and improving animal welfare. Int. J. Oncol. 29, 1493 1499.
138. Sun F.X., Tang Z.Y., Lui K.D. et al. (1996) Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int. J. Cancer 66, 239 243.
139. Tada M., Omata M., Ohto M. (1990) Analysis of Ras gene-mutations in human hepatic malignant-tumors by polymerase chain-reaction and direct sequencing. Cancer Res. 50, 1121 1124.
140. Takada S., Tsuchida N., Kobayashi M., Koike K. (1995) Disruption of the function of tumor-suppressor gene P53 by the Hepatitis-B Virus X-Protein and Hepatocarcinogenesis. J. Cancer Res. Clin. Oncol. 121, 593 601.
141. Takashima K., Ito Y., Gonzalez F.J., Nakajima T. (2008) Different mechanisms of DEHP-induced hepatocellular adenoma tumorigenesis in wild-type and Ppar alpha-null mice. J. Occup. Health 50, 169 180.
142. Tanaka N., Moriya K., Kiyosawa K., Koike K., Aoyama T. (2008) Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice: Implications for HCV-associated hepatocarcinogenesis. Int. J. Cancer 122, 124 131.
143. Tarsetti F., Lenzi R., Salvi R. et al. (1993) Liver carcinogenesis associated with feeding of ethionine in a choline-free diet: evidence against a role of oval cells in the emergence of hepatocellular carcinoma. Hepatology 18, 596 603.
144. Tennant B.C., Toshkov I.A., Peek S.F. et al. (2004) Hepatocellular carcinoma in the woodchuck model of hepatitis B virus infection. Gastroenterology 127, S283 293.
145. Teoh N.C., Dan Y.Y., Swisshelm K. et al. (2008) Defective DNA strand break repair causes chromosomal instability and accelerates liver carcinogenesis in mice. Hepatology 47, 2078 2088.
146. Terradillos O., Billet O., Renard C.A. et al. (1997) The hepatitis B virus X gene potentiates c-myc-induced liver oncogenesis in transgenic mice. Oncogene 14, 395 404.
147. Thieringer F., Maass T., Czochra P. et al. (2008) Spontaneous hepatic fibrosis in transgenic mice overexpressing PDGF-A. Gene 423, 23 28.
148. Thorgeirsson S.S. SantoniRugiu E. (1996) Transgenic mouse models in carcinogenesis: Interaction of c-myc with transforming growth factor alpha and hepatocyte growth factor in hepatocarcinogenesis. Br. J. Clin. Pharmacol. 42, 43 52.
149. Tonjes R.R., Lohler J., Osullivan J.F. et al. (1995) Autocrine mitogen Igegf cooperates with C-Myc or with the Hcs locus during hepatocarcinogenesis in transgenic mice. Oncogene 10, 765 768.
150. Tsukuma H., Hiyama T., Tanaka S. et al. (1993) Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N. Engl. J. Med. 328, 1797 1801. (Pubitemid 23174709)
151. Tuveson D.A., Jacks T. (2002) Technologically advanced cancer modeling in mice. Curr. Opin. Genet. Dev. 12, 105 110.
152. Valko M., Rhodes C.J., Moncol J., Izakovic M., Mazur M. (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact. 160, 1 40.
153. Verna L., Whysner J., Williams G.M. (1996) N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol. Ther. 71, 57 81. (Pubitemid 26323290)
154. Vesselinovitch S.D. Mihailovich N. (1983) Kinetics of diethylnitrosamine hepatocarcinogenesis in the infant mouse. Cancer Res. 43, 4253 4259.
155. Vesselinovitch S.D., Mihailovich N., Rao K.V.N. (1978) Morphology and metastatic nature of induced hepatic nodular lesions in C57bl X C3h F1 mice. Cancer Res. 38, 2003 2010.
156. Wang J.S. Groopman J.D. (1999) DNA damage by mycotoxins. Mutat. Res. Fundam. Mol. Mech. Mutagen. 424, 167 181.
157. Wang J. Liu X.M. (2007) Contamination of aflatoxins in different kinds of foods in China. Biomed. Environ. Sci. 20, 483 487.
158. Wang Z.Y., Agarwal R., Khan W.A., Mukhtar H. (1992) Protection against Benzo[a]Pyrene-induced and N-Nitrosodiethylamine-induced lung and forestomach tumorigenesis in a/J mice by water extracts of green tea and licorice. Carcinogenesis 13, 1491 1494.
159. Wang Q., Lin Z.Y., Feng X.L. (2001) Alterations in metastatic properties of hepatocellular carcinoma cell following H-ras oncogene transfection. World J. Gastroenterol. 7, 335 339.
160. Watanabe S., Horie Y., Kataoka E. et al. (2007) Non-alcoholic steatohepatitis and hepatocellular carcinoma: lessons from hepatocyte-specific phosphatase and tensin homolog (PTEN)-deficient mice. J. Gastroenterol. Hepatol. 22, S96 S100.
161. Watson R.E. Goodman J.I. (2002) Effects of phenobarbital on DNA methylation in GC-rich regions of hepatic DNA from mice that exhibit different levels of susceptibility to liver tumorigenesis. Toxicol. Sci. 68, 51 58.
162. Waxman D.J. Azaroff L. (1992) Phenobarbital induction of cytochrome P-450 gene expression. Biochem. J. 281 (Pt 3 577 592.
163. Weghorst C.M. Klaunig J.E. (1989) Phenobarbital promotion in diethylnitrosamine-initiated infant B6c3f1 mice - influence of gender. Carcinogenesis 10, 609 612.
164. Weisburger E.K. (1977) Carcinogenicity studies on halogenated hydrocarbons. Environ. Health Perspect. 21, 7 16.
165. Williams A.O. Knapton A.D. (1996) Hepatic silicosis, cirrhosis, and liver tumors in mice and hamsters: studies of transforming growth factor beta expression. Hepatology 23, 1268 1275.
166. Williams G.M., Iatropoulos M.J., Jeffrey A.M. (2000) Mechanistic basis for nonlinearities and thresholds in rat liver carcinogenesis by the DNA-reactive carcinogens 2-acetylaminofluorene and diethylnitrosamine. Toxicol. Pathol. 28, 388 395.
167. Wu C.G., Salvay D.M., Forgues M. et al. (2001) Distinctive gene expression profiles associated with Hepatitis B virus x protein. Oncogene 20, 3674 3682.
168. Xiong J., Yao Y.C., Zi X.Y. et al. (2003) Expression of hepatitis B virus X protein in transgenic mice. World J. Gastroenterol. 9, 112 116. (Pubitemid 36131290)
169. Yeldandi A.V., Rao M.S., Reddy J.K. (2000) Hydrogen peroxide generation in peroxisome proliferator-induced oncogenesis. Mutat. Res. Fundam. Mol. Mech. Mutagen. 448, 159 177.
170. Zhang G.J., Chen T.B., Bednar B. et al. (2007) Optical imaging of tumor cells in hollow fibers: evaluation of the antitumor activities of anticancer drugs and target validation. Neoplasia 9, 652 661.
171. Zhao W.L., Iskandar S., Kooshki M., Sharpe J.G., Payne V., Robbins M.E. (2007) Knocking out peroxisome proliferator-activated receptor (PPAR) alpha inhibits radiation-induced apoptosis in the mouse kidney through activation of NF-kappa B and increased expression of IAPs. Radiat. Res. 167, 581 591.
172. Zheng Y.Y., Chen W.L., Louie S.G., Yen T.S.B., Ou J.H.J. (2007) Hepatitis B virus promotes hepatocarcinogenesis in transgenic mice. Hepatology 45, 16 21.
173. Zhu H.Z., Wang Y., Chen J.Q., Cheng G.X., Xue J.L. (2004) Transgenic mice expressing hepatitis B virus X protein are more susceptible to carcinogen induced hepatocarcinogenesis. Exp. Mol. Pathol. 76, 44 50.
174. Zimmers T.A., Jin X.L., Gutierrez J.C. et al. (2008) Effect of in vivo loss of GDF-15 on hepatocellular carcinogenesis. J. Cancer Res. Clin. Oncol. 134, 753 759.