Helicobacter -Based Mouse Models of Digestive System Carcinogenesis

  • Arlin B. Rogers
  • JeanMarie Houghton
Part of the Methods in Molecular Biology™ book series (MIMB, volume 511)


Animal models are necessary to reproduce the complex host, microbial and environmental influences associated with infectious carcinogenesis of the digestive system. Today, mouse models are preferred by most researchers because of cost efficiencies, rapid reproduction, choice of laboratory reagents, and availability of genetically engineered mutants to study specific gene functions in vivo. Mouse models have validated the once-provocative hypothesis that Helicobacter pylori infection is a major risk factor for gastric carcinoma, dispelling early skepticism over the pathogenic nature of this organism in the human stomach. Enterohepatic Helicobacter spp. induce inflammatory bowel disease and colorectal carcinoma in susceptible mouse strains, permitting study of host immunity and microbial factors at the cellular and molecular level. H. hepaticus is the only proven infectious hepatocarcinogen of mice and has been used to explore mechanisms of inflammation-associated liver cancer as seen in human chronic viral hepatitis. For example, this model was used to identify for the first time a potential mechanism for male-predominant liver cancer risk independent of circulating sex hormones. Helicobacter-based mouse models of digestive system carcino-genesis are used to investigate the basic biology of inflammation-associated human cancers and to evaluate therapeutic interventions at the discovery level. Because of exciting advances in genetic engineering of mice, in vivo imaging, and system-wide genomics and proteomics, these models will provide even more information in the future. This chapter introduces the mouse as a model species; summarizes important models of inflammation-associated cancer incited by murine Helicobacter infection; and describes methods for the collection, sampling, and histologic grading of mouse digestive system tissues.

Key words

Carcinogenesis Digestive system neoplasms Inflammation Helicobacter infections Helicobacter pylori Helicobacter hepaticus Mice Disease models Animal 


  1. 1.
    Shibuya, K., Mathers, C. D., Boschi-Pinto, C., Lopez, A. D., and Murray, C. J. (2002) Global and regional estimates of cancer mortality and incidence by site: II. Results for the global burden of disease 2000.BMC Cancer2, 37.CrossRefPubMedGoogle Scholar
  2. 2.
    Bleich, A. and Mahler, M. (2005) Environment as a critical factor for the pathogen-esis and outcome of gastrointestinal disease: experimental and human inflammatory bowel disease andHelicobacter-induced gastritis.Pathobiology72, 293–307.CrossRefPubMedGoogle Scholar
  3. 3.
    Parkin, D. M. (2006) The global health burden of infection-associated cancers in the year 2002.Int J Cancer118, 3030–3044.CrossRefPubMedGoogle Scholar
  4. 4.
    Rogers, A. B. and Fox, J. G. (2004) Inflammation and cancer. I. Rodent models of infectious gastrointestinal and liver cancer.Am J Phys-iol Gastrointest Liver Physiol286, G361–366.CrossRefGoogle Scholar
  5. 5.
    Fox, J. G. and Wang, T. C. (2007) Inflammation, atrophy, and gastric cancer.J Clin Invest117, 60–69.CrossRefPubMedGoogle Scholar
  6. 6.
    Zhang, L. and Mitchell, H. (2006) The roles of mucus-associated bacteria in inflammator y bowel disease.Drugs Today (Barc)42, 605–616.CrossRefPubMedGoogle Scholar
  7. 7.
    Waterston, R. H., Lindblad-Toh, K., Birney, E., Rogers, J., Abril, J. F., Agarwal, P., et al. (2002) Initial sequencing and comparative analysis of the mouse genome.Nature420, 520–562.CrossRefPubMedGoogle Scholar
  8. 8.
    Syder, A. J., Oh, J. D., Guruge, J. L., O'Donnell, D., Karlsson, M., Mills, J. C., et al. (2003) The impact of parietal cells onHelicobacter pyloritropism and host pathology: an analysis using gnotobiotic normal and transgenic mice.Proc Natl Acad Sci USA100, 3467–3472.CrossRefPubMedGoogle Scholar
  9. 9.
    Rogers, A. B., Theve, E. J., Feng, Y., Fry, R. C., Taghizadeh, K., Clapp, K. M., et al. (2007) Hepatocellular carcinoma associated with liver-gender disruption in male mice.Cancer Res67, 11536–11546.CrossRefPubMedGoogle Scholar
  10. 10.
    Backhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A., and Gordon, J. I. (2005) Host-bacterial mutualism in the human intestine.Science307, 1915–1920.CrossRefPubMedGoogle Scholar
  11. 11.
    Maurer, K. J., Ihrig, M. M., Rogers, A. B., Ng, V., Bouchard, G., Leonard, M. R., et al. (2005) Identification of cholelithogenic enterohepaticHelicobacterspecies and their role in murine cholesterol gallstone formation.Gastroentero-logy128, 1023–1033.CrossRefGoogle Scholar
  12. 12.
    Moss, S. F. and Malfertheiner, P. (2007)Heli-cobacterand gastric malignancies.Helicobacter12(1), 23–30.CrossRefPubMedGoogle Scholar
  13. 13.
    Fox, J. G., Rogers, A. B., Ihrig, M., Taylor, N. S., Whary, M. T., Dockray, G., et al. (2003)Helicobacter pylori-associated gastric cancer in INS-GAS mice is gender specific.Cancer Res63, 942–950.PubMedGoogle Scholar
  14. 14.
    Fox, J. G., Wang, T. C., Rogers, A. B., Pou-tahidis, T., Ge, Z., Taylor, N., et al. (2003) Host and microbial constituents influenceHelicobacter pylori-induced cancer in a murine model of hypergastrinemia.Gastroenterology124, 1879–1890.CrossRefPubMedGoogle Scholar
  15. 15.
    Fox, J. G., Rogers, A. B., Whary, M. T., Ge, Z., Ohtani, M., Jones, E. K., et al. (2007) Accelerated Progression of gastritis to dysplasia in the pyloric antrum of TFF2−/−C57BL6 x Sv129Helicobacter pylori-infected mice.Am J Pathol171, 1520–1528.CrossRefPubMedGoogle Scholar
  16. 16.
    Whar y, M. T. and Fox, J. G. (2004) Th1-mediated pathology in mouse models of human disease is ameliorated by concurrent Th2 responses to parasite antigens.Curr Top Med Chem4, 531–538.Google Scholar
  17. 17.
    Lee, A., O'Rourke, J., and Enno, A. (2000) Gastric mucosa-associated lymphoid tissue lymphoma: implications of animal models on pathogenic and therapeutic considerations– mouse models of gastric lymphoma.Recent Results Cancer Res156, 42–51.PubMedGoogle Scholar
  18. 18.
    Lee, A., Fox, J. G., Otto, G., and Murphy, J. (1990) A small animal model of humanHelicobacter pyloriactive chronic gastritis.Gastroenterology99, 1315–1323.PubMedGoogle Scholar
  19. 19.
    De Bock, M., D'Herde, K., Duchateau, L., Hellemans, A., Decostere, A., Haesebrouck, F., et al. (2006) The effect ofHelicobacter felisandHelicobacter bizzozeroniion the gastric mucosa in Mongolian gerbils: a sequential pathological study.J Comp Pathol135, 226–236.CrossRefPubMedGoogle Scholar
  20. 20.
    Gasbarrini, A., Carloni, E., Gasbarrini, G., and Menard, A. (2003)Helicobacter pyloriand extragastric diseases – otherHelicobacters.Helicobacter8(1), 68–76.CrossRefPubMedGoogle Scholar
  21. 21.
    McCracken, V. J., Martin, S. M., and Lorenz, R. G. (2005) TheHelicobacter felismodel of adoptive transfer gastritis.Immunol Res33, 183–194.CrossRefPubMedGoogle Scholar
  22. 22.
    Fox, J. G., Sheppard, B. J., Dangler, C. A., Whary, M. T., Ihrig, M., and Wang, T. C. (2002) Germ-line p53-targeted disruption inhibits helicobacter-induced premalignant lesions and invasive gastric carcinoma through down- regulation of Th1 proinflammatory responses.Cancer Res62, 696–702.PubMedGoogle Scholar
  23. 23.
    Fox, J. G., Blanco, M., Murphy, J. C., Taylor, N. S., Lee, A., Kabok, Z., et al. (1993) Local and systemic immune responses in murineHelicobacter felisactive chronic gastritis.Infect Immun61, 2309–2315.PubMedGoogle Scholar
  24. 24.
    Lee, A., Hazell, S. L., O'Rourke, J., and Kou-prach, S. (1988) Isolation of a spiral-shaped bacterium from the cat stomach.Infect Immun56, 2843–2850.PubMedGoogle Scholar
  25. 25.
    Mohammadi, M., Redline, R., Nedrud, J., and Czinn, S. (1996) Role of the host in patho-genesis ofHelicobacter-associated gastritis:H. felisinfection of inbred and congenic mouse strains.Infect Immun64, 238–245.PubMedGoogle Scholar
  26. 26.
    Fox, J. G., Beck, P., Dangler, C. A., Whary, M. T., Wang, T. C., Shi, H. N., et al. (2000) Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reducesHelicobacter-induced gastric atrophy.Nat Med6, 536–542.CrossRefPubMedGoogle Scholar
  27. 27.
    Stoicov, C., Whary, M., Rogers, A. B., Lee, F. S., Klucevsek, K., Li, H., et al. (2004) Coinfec-tion modulates inflammatory responses and clinical outcome ofHelicobacter felisandToxoplasma gondiiinfections.J Immunol173, 3329–3336.PubMedGoogle Scholar
  28. 28.
    Fox, J. G. and Lee, A. (1993) Gastric helico-bacter infection in animals: natural and experimental infections. In Biology and Clinical Practice (Goodwin, C. and Worsley, B., eds), pp. 407–430, CRC Press, Boca Raton.Google Scholar
  29. 29.
    Lee, A., O'Rourke, J., De Ungria, M. C., Robertson, B., Daskalopoulos, G., and Dixon, M. F. (1997) A standardized mouse model ofHelico-bacter pyloriinfection: introducing the Sydney strain.Gastroenterology112, 1386–1397.CrossRefPubMedGoogle Scholar
  30. 30.
    Rogers, A. B., Taylor, N. S., Whary, M. T., Stefanich, E. D., Wang, T. C., and Fox, J. G. (2005)Helicobacter pyloribut not high salt induces gastric intraepithelial neoplasia in B6129 mice.Cancer Res65, 10709–10715.CrossRefPubMedGoogle Scholar
  31. 31.
    Peek, R. M., Jr. and Blaser, M. J. (2002)Heli-cobacter pyloriand gastrointestinal tract aden-ocarcinomas.Nat Rev Cancer2, 28–37.CrossRefPubMedGoogle Scholar
  32. 32.
    Pritchard, D. M. and Przemeck, S. M. (2004) Review article: how useful are the rodent animal models of gastric adenocarcinoma?Aliment Pharmacol Ther19, 841–859.CrossRefPubMedGoogle Scholar
  33. 33.
    Friis-Hansen, L., Rieneck, K., Nilsson, H. O., Wadstrom, T., and Rehfeld, J. F. (2006) Gastric inflammation, metaplasia, and tumor development in gastrin-deficient mice.Gastro-enterology131, 246–258.CrossRefGoogle Scholar
  34. 34.
    Wang, T. C., Dangler, C. A., Chen, D., Gold-enring, J. R., Koh, T., Raychowdhury, R., et al. (2000) Synergistic interaction between hypergastrinemia andHelicobacterinfection in a mouse model of gastric cancer.Gastroenter-ology118, 36–47.CrossRefGoogle Scholar
  35. 35.
    Stenstrom, B., Zhao, C. M., Rogers, A. B., Nilsson, H. O., Sturegard, E., Lundgren, S., et al. (2007) Swedish moist snuff accelerates gastric cancer development inHelicobacter pylori-infected wild-type and gastrin trans-genic mice.Carcinogenesis28(9), 2041–2046CrossRefPubMedGoogle Scholar
  36. 36.
    Ohtani, M., Garcia, A., Rogers, A. B., Ge, Z., Taylor, N. S., Xu, S., et al. (2007) Protective role of 17{beta}-estradiol against the development ofHelicobacter pylori-induced gastric cancer in INS-GAS mice.Carcinogenesis28, 2597–2604.CrossRefPubMedGoogle Scholar
  37. 37.
    Kuzushita, N., Rogers, A. B., Monti, N. A., Whary, M. T., Park, M. J., Aswad, B. I., et al. (2005) p27kip1 deficiency confers susceptibility to gastric carcinogenesis inHelicobacter pylori-infected mice.Gastroenterology129, 1544–1556.CrossRefPubMedGoogle Scholar
  38. 38.
    Xia, H. H., Yang, Y., Lam, S. K., Wong, W. M., Leung, S. Y., Yuen, S. T., et al. (2004) Aberrant epithelial expression of trefoil family factor 2 and mucin 6 inHelicobacter pyloriinfected gastric antrum, incisura, and body and its association with antralisation.J Clin Pathol57, 861–866.CrossRefPubMedGoogle Scholar
  39. 39.
    Nomura, S., Baxter, T., Yamaguchi, H., Leys, C., Vartapetian, A. B., Fox, J. G., et al. (2004) Spasmolytic polypeptide expressing metaplasia to preneoplasia inH. felis-infected mice.Gastroenterology127, 582–594.CrossRefPubMedGoogle Scholar
  40. 40.
    Kang, W., Rathinavelu, S., Samuelson, L. C., and Merchant, J. L. (2005) Interferon gamma induction of gastric mucous neck cell hypertrophy.Lab Invest85, 702–715.CrossRefPubMedGoogle Scholar
  41. 41.
    Goldenring, J. R. and Nomura, S. (2006) Differentiation of the gastric mucosa III. Animal models of oxyntic atrophy and metaplasia.Am J Physiol Gastrointest Liver Physiol291, G999–1004.CrossRefPubMedGoogle Scholar
  42. 42.
    Kurt-Jones, E. A., Cao, L., Sandor, F., Rogers, A. B., Whary, M. T., Nambiar, P. R., et al. (2007) Trefoil family factor 2 is expressed in murine gastric and immune cells and controls both gastrointestinal inflammation and systemic immune responses.Infect Immun75, 471–480.CrossRefPubMedGoogle Scholar
  43. 43.
    Farrell, J. J., Taupin, D., Koh, T. J., Chen, D., Zhao, C. M., Podolsky, D. K., et al. (2002) TFF2/SP-deficient mice show decreased gastric proliferation, increased acid secretion, and increased susceptibility to NSAID injury.J Clin Invest109, 193–204.PubMedGoogle Scholar
  44. 44.
    Correa, P. (1985) Mechanisms of gastric carcino-genesis. In Diet and Human Carcinogenesis (Joosens, J., et al., eds), pp. 109–115, Elsevier, Amsterdam.Google Scholar
  45. 45.
    Correa, P. and Houghton, J. (2007) Carcino-genesis ofHelicobacter pylori.Gastroenterology133, 659–672.CrossRefPubMedGoogle Scholar
  46. 46.
    Stolte, M. and Meining, A. (2001) The updated Sydney system: classification and grading of gastritis as the basis of diagnosis and treatment.Can J Gastroenterol15, 591–598.PubMedGoogle Scholar
  47. 47.
    Ming, S.-C. and Hirota, T. (1998) Malignant epithelial tumors of the stomach. In Pathology of the Gastrointestinal Tract (2nd edn) (Ming, S.-C. and Goldman, H., eds), pp. 607–650, Williams & Wilkins, Baltimore.Google Scholar
  48. 48.
    Boivin, G. P., Washington, K., Yang, K., Ward, J. M., Pretlow, T. P., Russell, R., et al. (2003) Pathology of mouse models of intestinal cancer: consensus report and recommendations.Gas-troenterology124, 762–777.CrossRefGoogle Scholar
  49. 49.
    Ward, J. M., Yoon, M., Anver, M. R., Haines, D. C., Kudo, G., Gonzalez, F. J., et al. (2001) Hyalinosis and Ym1/Ym2 gene expression in the stomach and respiratory tract of 129S4/ SvJae and wild-type and CYP1A2-null B6, 129 mice.Am J Pathol158, 323–332.CrossRefPubMedGoogle Scholar
  50. 50.
    Haines, D. C., Chattopadhyay, S., and Ward, J. M. (2001) Pathology of aging B6;129 mice.Toxicol Pathol29, 653–661.CrossRefPubMedGoogle Scholar
  51. 51.
    Cardiff, R. D., Ward, J. M., and Barthold, S. W. (2007) ‘One medicine-one pathology’: are veterinary and human pathology prepared?Lab Invest88(1), 18–26.CrossRefPubMedGoogle Scholar
  52. 52.
    Houghton, J., Stoicov, C., Nomura, S., Rogers, A. B., Carlson, J., Li, H., et al. (2004) Gastric cancer originating from bone marrow-derived cells.Science306, 1568–1571.CrossRefPubMedGoogle Scholar
  53. 53.
    Cendan, J. C. and Behrns, K. E. (2007) Associated neoplastic disease in inflammatory bowel disease.Surg Clin North Am87, 659–672.CrossRefPubMedGoogle Scholar
  54. 54.
    Taylor, N. S., Xu, S., Nambiar, P., Dewhirst, F. E., and Fox, J. G. (2007) EnterohepaticHelicobacterspecies are prevalent in mice from commercial and academic institutions in Asia, Europe, and North America.J Clin Microbiol45, 2166–2172.CrossRefPubMedGoogle Scholar
  55. 55.
    Dieleman, L. A., Arends, A., Tonkonogy, S. L., Goerres, M. S., Craft, D. W., Grenther, W., et al. (2000)Helicobacter hepaticusdoes not induce or potentiate colitis in interleukin-10-deficient mice.Infect Immun68, 5107–5113.CrossRefPubMedGoogle Scholar
  56. 56.
    Takaishi, H., Matsuki, T., Nakazawa, A., Takada, T., Kado, S., Asahara, T., et al. (2007) Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease.Int J Med Micro-biol298(5–6), 463–472.Google Scholar
  57. 57.
    Suerbaum, S., Josenhans, C., Sterzenbach, T., Drescher, B., Brandt, P., Bell, M., et al. (2003) The complete genome sequence of the carcinogenic bacteriumHelicobacter hepaticus.Proc Natl Acad Sci USA100, 7901–7906.CrossRefPubMedGoogle Scholar
  58. 58.
    Kuhn, R., Lohler, J., Rennick, D., Rajewsky, K., and Muller, W. (1993) Interleukin-10-de-ficient mice develop chronic enterocolitis.Cell75, 263–274.CrossRefPubMedGoogle Scholar
  59. 59.
    Maggio-Price, L., Treuting, P., Zeng, W., Tsang, M., Bielefeldt-Ohmann, H., and Iritani, B. M. (2006)Helicobacterinfection is required for inflammation and colon cancer in SMAD3-defi-cient mice.Cancer Res66, 828–838.CrossRefPubMedGoogle Scholar
  60. 60.
    Baumgart, D. C., Olivier, W. A., Reya, T., Peritt, D., Rombeau, J. L., and Carding, S. R. (1998) Mechanisms of intestinal epithelial cell injury and colitis in interleukin 2 (IL2)-deficient mice.Cell Immunol187, 52–66.CrossRefPubMedGoogle Scholar
  61. 61.
    Mombaerts, P., Mizoguchi, E., Grusby, M. J., Glimcher, L. H., Bhan, A. K., and Ton-egawa, S. (1993) Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice.Cell75, 274–282.CrossRefPubMedGoogle Scholar
  62. 62.
    Rudolph, U., Finegold, M. J., Rich, S. S., Har-riman, G. R., Srinivasan, Y., Brabet, P., et al. (1995) Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice.Nat Genet10, 143–150.CrossRefPubMedGoogle Scholar
  63. 63.
    Engle, S. J., Ormsby, I., Pawlowski, S., Boivin, G. P., Croft, J., Balish, E., et al. (2002) Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice.Cancer Res62, 6362–6366.PubMedGoogle Scholar
  64. 64.
    Maggio-Price, L., Bielefeldt-Ohmann, H., Treuting, P., Iritani, B. M., Zeng, W., Nicks, A., et al. (2005) Dual infection withHeli-cobacter bilisandHelicobacter hepaticusin p-glycoprotein-deficient mdr1a−/−mice results in colitis that progresses to dysplasia.Am J Pathol166, 1793–1806.CrossRefPubMedGoogle Scholar
  65. 65.
    Erdman, S. E., Poutahidis, T., Tomczak, M., Rogers, A. B., Cormier, K., Plank, B., et al. (2003) CD4(+) CD25(+) regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice.Am J Pathol162, 691–702.CrossRefPubMedGoogle Scholar
  66. 66.
    Berg, D. J., Davidson, N., Kuhn, R., Muller, W., Menon, S., Holland, G., et al. (1996) Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses.J Clin Invest98, 1010–1020.CrossRefPubMedGoogle Scholar
  67. 67.
    Erdman, S. E., Rao, V. P., Poutahidis, T., Ihrig, M. M., Ge, Z., Feng, Y., et al. (2003) CD4(+) CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogen-esis in mice.Cancer Res63, 6042–6050.PubMedGoogle Scholar
  68. 68.
    Itzkowitz, S. H. and Yio, X. (2004) Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation.Am J Physiol Gastrointest Liver Physiol287, G7–17.CrossRefPubMedGoogle Scholar
  69. 69.
    Winawer, S. J., Zauber, A. G., Fletcher, R. H., Stillman, J. S., O'Brien, M. J., Levin, B., et al. (2006) Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.Gas-troenterology130, 1872–1885.CrossRefGoogle Scholar
  70. 70.
    Mast, E. E., Alter, M. J., and Margolis, H. S. (1999) Strategies to prevent and controlHepatitis BandCvirus infections: a global perspective.Vaccine17, 1730–1733.CrossRefPubMedGoogle Scholar
  71. 71.
    Dandri, M., Lutgehetmann, M., Volz, T., and Petersen, J. (2006) Small animal model systems for studyingHepatitis Bvirus replication and pathogenesis.Semin Liver Dis26, 181–191.CrossRefPubMedGoogle Scholar
  72. 72.
    Perz, J. F., Armstrong, G. L., Farrington, L. A., Hutin, Y. J., and Bell, B. P. (2006) The contributions ofHepatitis Bvirus andHepatitis Cvirus infections to cirrhosis and primary liver cancer worldwide.J Hepatol45, 529–538.CrossRefPubMedGoogle Scholar
  73. 73.
    El-Serag, H. B. and Rudolph, K. L. (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis.Gastroenterology132, 2557–2576.CrossRefPubMedGoogle Scholar
  74. 74.
    Chaimuangraj, S., Thamavit, W., Tsuda, H., and Moore, M. A. (2003) Experimental investigation of opisthorchiasis-associated cholan-giocarcinoma induction in the Syrian hamster – pointers for control of the human disease.Asian Pac J Cancer Prev4, 87–93.PubMedGoogle Scholar
  75. 75.
    Fox, J. G., Dewhirst, F. E., Tully, J. G., Paster, B. J., Yan, L., Taylor, N. S., et al. (1994)Heli-cobacter hepaticussp. nov., a microaerophilic bacterium isolated from livers and intestinal mucosal scrapings from mice.J Clin Microbiol32, 1238–1245.PubMedGoogle Scholar
  76. 76.
    Ward, J. M., Fox, J. G., Anver, M. R., Haines, D. C., George, C. V., Collins, M. J., Jr., et al. (1994) Chronic active hepatitis and associated liver tumors in mice caused by a persistent bacterial infection with a novelHelicobacterspecies.J Natl Cancer Inst86, 1222–1227.CrossRefPubMedGoogle Scholar
  77. 77.
    Ward, J. M., Anver, M. R., Haines, D. C., and Benveniste, R. E. (1994) Chronic active hepatitis in mice caused byHelicobacter hepaticus.Am J Pathol145, 959–968.PubMedGoogle Scholar
  78. 78.
    Canella, K. A., Diwan, B. A., Gorelick, P. L., Donovan, P. J., Sipowicz, M. A., Kasprzak, K. S., et al. (1996) Liver tumorigenesis byHelico-bacter hepaticus: considerations of mechanism.In Vivo10, 285–292.PubMedGoogle Scholar
  79. 79.
    Leong, R. W. and Sung, J. J. (2002) Review article:Helicobacterspecies and hepatobiliary diseases.Aliment Pharmacol Ther16, 1037–1045.CrossRefPubMedGoogle Scholar
  80. 80.
    Whary, M. T. and Fox, J. G. (2006) Detection, eradication, and research implications ofHelicobacterinfections in laboratory rodents.Lab Anim (NY)35, 25–27, 30–26.CrossRefGoogle Scholar
  81. 81.
    Nyska, A., Maronpot, R. R., Eldridge, S. R., Haseman, J. K., and Hailey, J. R. (1997) Alteration in cell kinetics in control B6C3F1 mice infected withHelicobacter hepaticus.Tox-icol Pathol25, 591–596.CrossRefGoogle Scholar
  82. 82.
    Hailey, J. R., Haseman, J. K., Bucher, J. R., Radovsky, A. E., Malarkey, D. E., Miller, R. T., et al. (1998) Impact ofHelicobacter hepaticusinfection in B6C3F1 mice from twelve National Toxicology Program two-year carcinogenesis studies.Toxicol Pathol26, 602–611.PubMedGoogle Scholar
  83. 83.
    Ihrig, M., Schrenzel, M. D., and Fox, J. G. (1999) Differential susceptibility to hepatic inflammation and proliferation in AXB recombinant inbred mice chronically infected withHelicobacter hepaticus.Am J Pathol155, 571–582.CrossRefPubMedGoogle Scholar
  84. 84.
    Singh, R., Leuratti, C., Josyula, S., Sipowicz, M. A., Diwan, B. A., Kasprzak, K. S., et al. (2001) Lobe-specific increases in malondial-dehyde DNA adduct formation in the livers of mice following infection withHelicobacter hepaticus.Carcinogenesis22, 1281–1287.CrossRefPubMedGoogle Scholar
  85. 85.
    Sipowicz, M. A., Chomarat, P., Diwan, B. A., Anver, M. A., Awasthi, Y. C., Ward, J. M., et al. (1997) Increased oxidative DNA damage and hepatocyte overexpression of specific cytochrome P450 isoforms in hepatitis of mice infected withHelicobacter hepaticus.Am J Pathol151, 933–941.PubMedGoogle Scholar
  86. 86.
    Sipowicz, M. A., Weghorst, C. M., Shiao, Y. H., Buzard, G. S., Calvert, R. J., Anver, M. R., et al. (1997) Lack of p53 and ras mutations inHelicobacter hepaticus-induced liver tumors in A/JCr mice.Carcinogenesis18, 233–236.CrossRefPubMedGoogle Scholar
  87. 87.
    Ramljak, D., Jones, A. B., Diwan, B. A., Per-antoni, A. O., Hochadel, J. F., and Anderson, L. M. (1998) Epidermal growth factor and transforming growth factor-alpha-associated overexpression of cyclin D1, Cdk4, and c-Myc during hepatocarcinogenesis inHelicobacter hepaticus-infected A/JCr mice.Cancer Res58, 3590–3597.PubMedGoogle Scholar
  88. 88.
    Diwan, B. A., Ward, J. M., Ramljak, D., and Anderson, L. M. (1997) Promotion byHeli-cobacter hepaticus-induced hepatitis of hepatic tumors initiated byN-nitrosodimethylamine in male A/JCr mice.Toxicol Pathol25, 597–605.CrossRefPubMedGoogle Scholar
  89. 89.
    Ward, J. M. (1997) Helicobacter infections of rodents and carcinogenesis bioassays.Toxicol Pathol25, 590.CrossRefPubMedGoogle Scholar
  90. 90.
    Fox, J. G., MacGregor, J. A., Shen, Z., Li, X., Lewis, R., and Dangler, C. A. (1998) Comparison of methods of identifyingHelicobacter hepaticusin B6C3F1 mice used in a carcinogen-esis bioassay.J Clin Microbiol36, 1382–1387.PubMedGoogle Scholar
  91. 91.
    Haseman, J. K., Hailey, J. R., and Morris, R. W. (1998) Spontaneous neoplasm incidences in Fischer 344 rats and B6C3F1 mice in two-year carcinogenicity studies: a National Toxicology Program update.Toxicol Pathol26, 428–441.CrossRefPubMedGoogle Scholar
  92. 92.
    Waxman, D. J. and O×Connor, C. (2006) Growth hormone regulation of sex-dependent liver gene expression.Mol Endocrinol20, 2613–2629.CrossRefPubMedGoogle Scholar
  93. 93.
    Boutin, S. R., Rogers, A. B., Shen, Z., Fry, R. C., Love, J. A., Nambiar, P. R., et al. (2004) Hepatic temporal gene expression profiling inHelicobacter hepaticus-infected A/JCr mice.Toxicol Pathol32, 678–693.CrossRefPubMedGoogle Scholar
  94. 94.
    Rogers, A. B., Boutin, S. R., Whary, M. T., Sundina, N., Ge, Z., Cormier, K., et al. (2004) Progression of chronic hepatitis and preneoplasia inHelicobacter hepaticus-infected A/JCr mice.Toxicol Pathol32, 668–677.CrossRefPubMedGoogle Scholar
  95. 95.
    O'Rourke, J. L., Grehan, M., and Lee, A. (2001) Non-pylori Helicobacter species in humans.Gut49, 601–606.CrossRefPubMedGoogle Scholar
  96. 96.
    Fox, J. (1998) EnterohepaticHelicobacters: natural and experimental models.Ital J Gas-troenterol Hepatol30(3), S264–269.Google Scholar
  97. 97.
    Maurer, K. J., Rogers, A. B., Ge, Z., Wiese, A. J., Carey, M. C., and Fox, J. G. (2006)Heli-cobacter pyloriand cholesterol gallstone formation in C57L/J mice: a prospective study.Am J Physiol Gastrointest Liver Physiol290, G175–182.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Arlin B. Rogers
  • JeanMarie Houghton

There are no affiliations available

Personalised recommendations