Intestinal metaplasia: The effect of acid on the gastric mucosa and gastric carcinogenesis

Journal of Toxicologic Pathology

Volumn 23, Issue 3, 2010, Pages 115-123

  Watanabe, Hiromitsu ^a  

^a HIROSHIMA UNIVERSITY   (Japan)

Author keywords

Gastric cancer; Glandular stomach; Intestinal metaplasia; Rat; X irradiation

Indexed keywords

1,2 DIMETHYLHYDRAZINE; 2 AMINO 1 METHYL 6 PHENYLIMIDAZO[4,5 B]PYRIDINE; ALKALINE PHOSPHATASE; AZOXYMETHANE; HISTAMINE; MERCAPTAMINE; METHYLNITRONITROSOGUANIDINE; METHYLNITROSOUREA; RANITIDINE; TRANSCRIPTION FACTOR CDX2;

ACHLORHYDRIA; CELL DIFFERENTIATION; DISEASE CLASSIFICATION; DUODENUM MUCOSA; GASTRECTOMY; GERBIL; HELICOBACTER INFECTION; HUMAN; INTESTINE METAPLASIA; MULTIPOTENT STEM CELL; NONHUMAN; RADIATION DOSE; RADIATION EXPOSURE; RAT STRAIN; REVIEW; SEX DIFFERENCE; SPECIES DIFFERENCE; STEM CELL; STOMACH ACID; STOMACH CANCER; STOMACH CARCINOGENESIS; STOMACH JUICE; STOMACH MUCOSA; STOMACH PH; STRAIN DIFFERENCE; SUBMANDIBULAR GLAND; TRANSGENIC MOUSE;

EID: 79953111826     PISSN: 09149198     EISSN: None     Source Type: Journal    
DOI: 10.1293/tox.23.115     Document Type: Review

References (92)

1. Slack JMW. Homoeotic transformations in man: implications for the mechanism of embryonic development and for the organization of epithelia. J Theor Biol. 114: 463- 490. 1985.
2. Leube RE and Rustad TJ. Squamous cell metaplasia in the human lung: molecular characteristics of epithelial stratification. Virchows Arch B Cell Pathol Incl Mol Pathol. 61: 227-253. 1991.
3. Kvist E, Sjølin KE, Laursen H, Orntoft TF, and Sturmer MA. Squamous cell metaplasia of the bladder urothelium. A retrospective study of 36 patients. APMIS. 100: 650-654. 1992.
4. Nepomnyashchikh GI, Aidagulova SV, Nepomnyashchikh DL, Boboev MM, Isaenko VI, Abdullaev NA, Ivaninskii OI, and Kunin IS. 67 stereotypes of structural modification of the urothelium in various diseases of the urinary bladder and prostate. Bull Exp Biol Med. 146: 415-419. 2008.
5. Spechler SJ. Intestinal metaplasia at the gastroesophageal junction. Gastroenterology. 126: 567-575. 2004.
6. Mann NS, Mann SK, and Rachut E. Heterotopic gastric tissue in the duodenal bulb. J Clin Gastroenterol. 30: 303- 306. 2000.
7. Morson BC. Intestinal metaplasia of gastric mucosa. Brit J Cancer. 9: 365-376. 1955.
8. Jarvi H and Lauren P. On the role of heterotopias of the intestinal epithelium in the pathogenesis of gastric cancer. Acta Pathol Microbiol Scand Supp1. 29: 26-43. 1951.
9. Nakamura K, Sugano H, and Takagi K. Carcinoma of the stomach in incipient phase: its histogenesis and histological appearances. Gann. 59: 251-258. 1968.
10. Rubin W, Ross LL, Jeffries GH, and Slessenger MH. Intestinal metaplasia and heterotopia: a fine structural study. Lab Invest. 15: 1024-1049. 1966.
11. Ming SC, Goldman H, and Freiman DC. Intestinal metaplasia and histogenesis of carcinoma in human stomach: light and electron microscopic study. Cancer. 20: 1418-1429. 1967.
12. Sugimura T, Kawachi T, Kogure K, Tokunaga A, Tanaka N, Sasajima K, Koyama Y, Hirota T, and Sano R. Enzymologic changes in abnormal differentiation-Intestinal metaplasia in human gastric mucosa-A possible precancerous changes. In: Differentiation and Control of Malignancy of Tumor Cells. W Nakahara, T Ono, T Sugimura, and H Sugano (eds). Univ. Park Press, Baltimore, MD. 251-263.
13. Teglbaerg PS and Nielsen HO. "Small intestinal type" and "colonic type" intestinal metaplasia of the human stomach. Acta Path Microbiol Scand Sect A. 86: 351-355. 1978.
14. Jass JR and Filipe MI. The mucin profiles of normal gastric mucosa, intestinal metaplasia and its variants gastric carcinoma. Histochem J. 23: 931-939. 1981.
15. Watanabe H, Naito M, and Ito A. The effect of sex difference on induction of intestinal metaplasia in rats. Acta Pathol Jpn. 34: 305-312. 1984.
16. Tsukamoto T, Mizoshita T, and Tatematsu M. Gastric-andintestinal mixed-type intestinal metaplasia: aberrant expression of transcr iption factors and stem cel l intestinalization. Gastric Cancer. 9: 156-166. 2006.
17. Watanabe H. Pathological studies on intestinal metaplasia- in particular references to acid of gastric mucosa and gastric tumorigenesis. Proc RINMB. 29: 193-216. 1988 (in Japanese).
18. Watanabe H. Experimentally induced intestinal metaplasia in Wistar rats by X-ray irradiation. Gastroenteology. 75: 796-799. 1978.
19. Watanabe H, Fujii I, and Tedara Y. Induction of intestinal metaplasia in the rat gastric mucosa by local X-irradiation. Pathol Res Pract. 170: 104-114. 1980.
20. Watanabe H, Naito M, Kawashima K, and Ito A. Intestinal metaplasia induced by X-irradiation in different strains of rats. Acta Pathol Jpn. 35: 841-847. 1985.
21. Watanabe H, Fujimoto N, Masaoka Y, Ohtaki M, and Ito A. Strain differences in the induction of intestinal metaplasia by X-irradiation in rats. J Gastroenterol. 32: 295-299. 1997.
22. Lu H, Shiraki K, Ishimura Y, Ohara M, Uesaka T, Katoh O, and Watanabe H. The morphological changes of gastric mucosa in Mongolian gerbils by X-irradiation. Nagasaki Med J. 75: 210-212. 2000 (in Japanese).
23. Watanabe H, Okamoto T, Matsuda M, Takahashi T, Ogundigie PO, and Ito A. Effects of sex hormones on induction of intestinal metaplasia by X-irradiation in rats. Acta Patho1 Jpn. 43: 456-463. 1993.
24. Watanabe H, Kamikawa M, Nakagawa Y, Takahashi T, and Ito A. The effects of ranitidine and cysteamine on intestinal metaplasia induced by X-irradiation in rats. Acta Pathol Jpn. 38: 1285-1296. 1988.
25. Beck F, Chawengsaksophak K, Waring P, Playford RJ, and Furness JB. Reprogramming of intestinal differentiation and intercalary regeneration in Cdx2 mutant mice. Proc Natl Acad Sci USA. 96: 7318-7323. 1999.
26. Phillips RW, Frierson HF Jr, and Moskaluk CA. Cdx2 as a marker of epithelial intestinal differentiation in the esophagus. Am J Surg Pathol. 27: 1442-1447. 2003.
27. Silberg DG, Sullivan J, Kang E, Swain GP, Moffett J, Sund NJ, Sackett SD, and Kaestner KH. Cdx2 ectopic expression induces gastric intestinal metaplasia in transgenic mice. Gastroenterology. 122: 689-696. 2002.
28. Tsukamoto T, Inada K, Tanaka H, Mizoshita T, Mihara M, Ushijima T, Yamamura Y, Nakamura S, and Tatematsu M. Down-regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdx1 and Cdx2: inverse correlation during progression from gastric/ intestinal-mixed to complete intestinal metaplasia. J Cancer Res Clin Oncol. 130: 135-145. 2004.
29. Shiotani A, Uedo N, Iishi H, Tatsuta M, Ishiguro S, Nakae Y, Kamada T, Haruma K, and Merchant JL. Re-expression of sonic hedgehog and reduction of CDX2 after Helicobacter pylori eradication prior to incomplete intestinal metaplasia. Int J Cancer. 121: 1182-1189. 2007.
30. Silberg DG, Furth EE, Taylor JK, Schuck T, Chiou T, and Traber PG. CDX1 protein expression in normal, metaplastic, and neoplastic human alimentary tract epithelium. Gastroenterology. 113: 478-486. 1997.
31. Almeida R, Silva E, Santos-Silva F, Silberg DG, Wang J, De Bolós C, and David L. Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. J Pathol. 199: 36-40. 2003.
32. Mutoh H, Sakurai S, Satoh K, Osawa H, Hakamata Y, Takeuchi T, and Sugano K. Cdx1 induced intestinal metaplasia in the transgenic mouse stomach: comparative study with Cdx2 transgenic mice. Gut. 53: 1416-1423. 2004.
33. Judd LM, Andringa A, Rubio CA, Spicer Z, Shull GE, and Miller ML. Gastric achlorhydria in H/K-ATPase-deficient (Atp4a(-/-)) mice causes severe hyperplasia, mucocystic metaplasia and upregulat ion of growth factors. J Gastroenterol Hepatol. 20: 1266-1278. 2005.
34. Li QL, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB, Kim HM, Kim WJ, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae SC, and Ito Y. Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell. 109: 113-124. 2002.
35. Fukamachi H, Mimata A, Tanaka I, Ito K, Ito Y, and Yuasa Y. In vitro differentiation of Runx3-/- p53-/- gastric epithelial cells into intestinal type cells. Cancer Sci. 99: 671-676. 2008.
36. Yuasa H, Inada K, Watanabe H, and Tatematsu M. A phenotypic shift from gastric-intestinal to solely intestinal cells types in intestinal metaplasia in rat stomach following treatment with X-rays. J Toxicol Pathol. 15: 85-93. 2002.
37. Marshall BJ and Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1(8390): 1311-1315. 1984.
38. Correa P, Haenszel W, Cuello C, Zavala D, Fontham E, Zarama G, Tannenbaum S, Collazos T, and Ruiz B. Gastric precancerous process in a high risk population: cohort follow-up. Cancer Res. 50: 4737-4740. 1990.
39. Correa P, Fontham ET, Bravo JC, Bravo LE, Ruiz B, Zarama G, Realpe JL, Malcom GT, Li D, Johnson WD, and Mera R. Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-Helicobacter pylori therapy. J Natl Cancer Inst. 92: 1881-1888. 2000.
40. Ito M, Haruma K, Kamada T, Mihara M, Kim S, Kitadai Y, Sumii M, Tanaka S, Yoshihara M, and Chayama K. Helicobacter pylori eradication therapy improves atrophic gastritis and intestinal metaplasia: a 5-year prospective study of patients with atrophic gastritis. Aliment Pharmacol Ther. 16: 1449-1456. 2002.
41. Haruma K, Mihara M, Okamoto E, Kusumoki H, Hananoki M, Tanaka S, Yoshihara M, Sumi K, and Kajiyama G. Eradication of Helicobacter pylori increases gastric acidity in patients with atrophic gastritis of the corpus. Evaluation of 24-h pH monitoring. Aliment Pharmacol Ther. 13: 155-162. 1999.
42. Kashiwagi H. Ulcers and gastritis. Endoscopy. 37: 110-115. 2005.
43. Wyatt JI, Rathbone BJ, Sobala GM, Shallcross T, Heatley RV, Axon AT, and Dixon MF. Gastric epithelium in the duodenum: its association with Helicobacter pylori and inflammation. J Clin Pathol. 43: 981-986. 1990.
44. Ford AC, Delaney BC, Forman D, and Moayyedi P. Eradication therapy in Helicobacter pylori positive peptic ulcer disease: systematic review and economic analysis. Am J Gastroenterol. 99: 1833-1855. 2004.
45. Hobsley M, Tovey FI, and Holton J. Controversies in the Helicobacter pylori/duodenal ulcer story. Trans R Soc Trop Med Hyg. 102: 1171-1175. 2008.
46. Hobsley M, Tovey FI, and Holton J. Precise role of H pylori in duodenal ulceration. World J Gastroenterol. 12: 6413- 6419. 2006.
47. Hirayama F, Takagi S, Yokoyama Y, Iwao E, and Ikeda Y. Establishment of gastric Helicobacter pylori infection in Mongolian gerbils. J Gastroenterol. 31 (Suppl 9): 24-28. 1996.
48. Elfvin A, Bölin I, Von Bothmer C, Stolte M, Watanabe H, Fändriks L, and Vieth M. Helicobacter pylori induces gast r i t is and intest inal metaplasia but no gast r ic adenocarcinoma in Mongol ian gerbi ls. Scand J Gastroenterol. 40: 1313-1320. 2005.
49. Sun YQ, Petersson F, Monstein HJ, Söderholm JD, Rehfeld JF, and Borch K. Long- term morpho- funct ional development of Helicobacter pylori-induced gastritis in Mongolian gerbils. Scand J Gastroenterol. 40: 1157-1167. 2005.
50. Nozaki K, Shimizu N, Tsukamoto T, Inada K, Cao X, Ikehara Y, Kaminishi M, Sugiyama A, and Tatematsu M. Reversibility of heterotopic proliferative glands in glandular stomach of Helicobacter pylori-infected Mongolian gerbils on eradication. Jpn J Cancer Res. 93: 374-381. 2002.
51. Tatematsu M, Tsukamoto T, and Mizoshita T. Role of Helicobacter pylori in gastric carcinogenesis: the origin of gastric cancers and heterotopic proliferative glands in Mongolian gerbils. Helicobacter. 10: 97-106. 2005.
52. Mizoshita T, Tsukamoto T, Takenaka Y, Cao X, Kato S, Kaminishi M, and Tatematsu M. Gastric and intestinal phenotypes and histogenesis of advanced glandular stomach cancers in carcinogen-treated, Helicobacter pylori-infected Mongolian gerbils. Cancer Sci. 97: 38-44, 2006.
53. Saito A, Shimoda T, Nakanishi Y, Ochiai A, and Toda G. Histologic heterogeneity and mucin phenotypic expression in early gastric cancer. Pathol Inter. 51: 165-171. 2001.
54. Ando Y, Uesaka T, Kido S, Fujimoto N, Tatematsu M, Ishimura Y, Shiraki K, Hirata S, Kuramoto K, Shoji S, Katoh O, and Watanabe H. No susceptibility of colon tissue implanted into the glandular stomach of rats to N-Nitroso-Nmethylurea (MNU) carcinogenesis. Oncol Rep. 5: 1373- 1376. 1998.
55. Dayal Y and Wolfe HJ. Gastrin-producing cells in ectopic gastric mucosa of developmental and metaplastic origins. Gastroenterology. 75: 655-660. 1978.
56. Ming SC. Cellular and molecular pathology of gastric carcinoma and precursor lesions: A critical review. Gastric Cancer. 1: 31-50. 1998.
57. Jovanovic I, Tzardi M, Mouzas IA, Micev M, Pesko P, Milosavijevic T, Zois M, Sganzos M, Delides G, and Kanavaros P. Changing pattern of cytokeratin 7 and 20 expression from normal epithelium to intestinal metaplasia of the gastric mucosa and gastroesophageal junction. Histol Histopathol. 17: 445-454. 2002.
58. Ciancio G, Nuti M, Orsini B, Iovi F, Ortolani M, Palomba A, Amorosi A, Surrenti E, Ilani SM, and Surrenti C. Regression of duodenal gastric metaplasia in Helicobacter pylori positive patients with duodenal ulcer disease. Dig Liver Dis. 34: 16-21, 2002.
59. Tanaka M, Saito H, Kusumi T, Fukuda S, Shimoyama T, Sasaki Y, Suto K, Munakata A, and Kudo H. Observer variation of diagnoses based on simple biopsy criteria differentiating among Crohn's disease, ulcerative colitis, and other forms of colitis. J Gastroenterol Hepatol. 16: 1353- 1359. 2001.
60. Cunliffe RN, Rose FR, Keyte J, Abberley L, Chan WC, and Mahida YR. Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease. Gut. 48: 176-185. 2001.
61. Yamada Y, Yoshimi N, Hirose Y, Matsunaga K, Katayama M, Sakata K, Shimizu M, Kuno T, and Mori H. Sequential analysis of morphological and biological properties of betacatenin- accumulated crypts, provable premalignant lesions independent o f aberrant crypt foci in rat colon carcinogenesis. Cancer Res. 61: 1874-1878. 2001.
62. Fujii I, Watanabe H, Naito M, Kawashima K, and Ito A. The induction of intestinal metaplasia in rats by pyloroplasty or pyloroplasty plus vagotomy. Pathol Res Pract. 180: 502-505. 1985.
63. Watanabe H, Okamoto T, Fudaba Y, Ogundigie PO, and Ito A. Influence of gastric pH modifiers on development of intestinal metaplasia induced by X-irradiation in rats. Jpn J Cancer Res. 84: 1037-1042. 1993.
64. Kinoshita K, Watanabe H, Ando Y, Katayama M, Yamamoto H, Hirano N, Yoshikuni S, and Yamamoto T. Effects of subtotal resection of the fundus on development of intestinal metaplasia induced by X-ray irradiation in Donryu rats. Pathol Int. 50: 879-883. 2000.
65. Watanabe H, Naito M, Kawashima K, and Ito A. PH-related differentiation in the epithelia of the gastric mucosa of postnatal rats. Acta Pathol Jpn. 35: 569-576. 1985.
66. Watanabe H, Ando Y, Uesaka T, Ishimura Y, Shiraki K, Lu H, Ohara M, Shoji S, and Katoh O. Grafting of stomach tissue into the duodenum in F344 rats results in chimeric crypts and tumor development. J Clin Exp Cancer Res. 19: 207-210. 2000.
67. Watanabe H, Ochiya T, Ueda S, Kominami Y, Gon R, Hayashi M, Nishiki M, Sasaki A, Shiraishi M, and Kamiya K. A rat model of heterototrophi transplantation into duodenum and liver. Surg Front. 15: 454-458. 2008 (in Japanese).
68. Yadirgi G and Marino S. Adult neural stem cells and their role in brain pathology. J Pathol. 217: 242-253. 2009.
69. Ratajczak MZ, Zuba-Surma EKB, and Machalinski KM. Bone-marrow-derived stem cells-our key to longevity? J Appl Genet. 48: 307-319. 2007.
70. Moshiri A, Close J, and Reh TA. Retinal stem cells and regeneration. Int J Dev Biol. 48: 1003-1014. 2004.
71. Duan X, Kang E, Liu CY, Ming GL, and Song H. Development of neural stem cell in the adult brain. Curr Opin Neurobiol. 18: 108-115. 2008.
72. Tiede S, Kloepper JE, Bodò E, Tiwari S, Kruse C, and Paus R. Hair follicle stem cells: walking the maze. Eur J Cell Biol.
73. Lou X, Zhang Y, and Yuan C. Multipotent stem cells from the young rat inner ear. Neurosci Lett. 416: 28-33, 2007.
74. Matsubara Y, Saito E, Suzuki H, Watanabe N, Murata M, and Ikeda Y. Generation of megakaryocytes and platelets from human subcutaneous adipose tissues. Biochem Biophys Res Commun. 378: 716-720. 2009.
75. Nishida K, Yamato M, Hayashida Y, Watanabe K, Yamamoto K, Adachi E, Nagai S, Kikuchi A, Maeda N, Watanabe H, Okano T, and Tano Y. Corneal reconstruction with tissue-engineered cell sheets composed of autologous oral mucosal epithelium. New Eng J Med. 351: 1187-1196. 2004.
76. Walkup MH and Gerber DA. Hepatic stem cells: in search of. Stem Cells. 24: 1833-1840, 2006.
77. Cao B and Huard J. Muscle-derived stem cells. Cell Cycle. 3: 104-107. 2004.
78. Fernandes KJ and Miller FD. Isolation, expansion, and differentiation of mouse skin-derived precursors. Methods Mol Biol. 482: 159-170. 2009.
79. Watanabe H, Ochiya T, Ueda S, Kominami Y, Gon R, Nishiki M, Hayashi M, Sasaki A, Shiraishi M, Kashimoto N, Myojin Y, and Kamiya K. Differentiation of a hepatic phenotype after heterotropic transplantation of heart, kidney, brain, and skin tissues into liver in F344 rats. Biochem Biophys Res Commun. 354: 841-845. 2007.
80. Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, and Grompe M. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nature Med. 5: 1229-1234. 2000.
81. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, and Goff JP. Bone marrow as a potential source of hepatic oval cells. Science. 284: 1168-1170. 1999.
82. Theise ND, Badve S, Saxena R, Henegariu O, Sell S, Crawford JM, and Krause DS. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology. 31: 235-240. 2000.
83. Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O, and Krause DS. Liver from bone marrow in humans. Hepatology. 32: 11-16. 2000.
84. Alison MR, Poulsom R, Jeffery R, Dhillon AP, Quaglia A, Jacob J, Novelli M, Prentice G, Williamson J, and Wright NA. Hepatocytes from non-hepatic adult stem cells. Nature. 406: 257. 2000.
85. Nakagawa Y, Ando Y, Fujimoto N, Masaoka Y, Tanizaki M, Shoji S, Katoh O, and Watanabe H. Colon tissue implanted into the glandular stomach in rats lacks susceptibility to Nmethyl- N' - n i tro-N-ni trosoguanidine MNNG) carcinogenesis. Oncol Rep. 4: 517-519. 1997.
86. Nakagawa Y, Watanabe H, Takahashi T, Ito A, and Dohi K. Carcinogenicity of 1,2-dimethylhydrazine in colorectal tissue heterotopically transplanted into the glandular stomach of rat. Jpn J Cancer Res. 83: 24-30. 1992.
87. Watanabe H and Ito A. Relationship between gastric tumorigenesis and intestinal metaplasia in rat given Xradiation and or N-methy1-N'-nitro-N-nitrosoguanidine. J Natl Cancer Inst. 76: 865-870. 1986.
88. Watanabe H, Ando Y, Yamada K, Okamoato T, and Ito A. Lack of any positive effects of intestinal metaplasia on induction of gastric tumors in Wistar rats treated with Nmethy1- N-nitrosourea in their drinking water. Jpn J Cancer Res. 85: 892-896. 1994.
89. Ando Y, Watanabe H, Tatematsu M, Hirano K, Furihata C, Fujimoto N, Toge T, and Ito A. Gastric tumorigenicity of 1,2-dimethylhydrazine on the background of gastric intestinal metaplasia induced by X-irradiation in CD(SD) rats. Jpn J Cancer Res. 87: 433-436. 1996.
90. Watanabe H, Uesaka T, Kido S, Ishimura Y, Shiraki K, Kuramoto K, Hirata S, Shoji S, Katoh O, and Fujimoto N. Gastric tumor induction by 1,2-dimethylhydrazine in Wistar rats with intestinal metaplasia caused by X-irradiation. Jpn J Cancer Res. 90: 1207-1211. 1999.
91. Watanabe H, Fujimoto N, Masaoka Y, Kurosumi M, Oguri T, Takahashi T, Kido S, Hirata S, Kuramoto K, Shoji S, and Katoh O. Effects of azoxymethane on X-ray induced intestinal metaplasia in Donryu rats. Oncol Rep. 5: 837-840. 1998.
92. Kashiwabara S, Kashimoto N, Uesaka T, Wakabayashi K, Kamiya K, and Watanabe H. Tumor induct ion by azoxymethane (AOM) and 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine (PhIP) in F344 rat gastric mucosa featuring intestinal metaplasia caused by Xirradiation. J Exp Clin Cancer Res. 24: 305-312.