| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Pediatrics [E. E. M., X-J. Z., M. J. S. M.] and Pathology [B. R., E. T. H. F., R. M., P. C.], Stanley Scott Cancer Center, Louisiana State University Medical Center, New Orleans, Louisiana 70112; Universidad del Valle, Cali [L. E. B.], and Hospital Departmental, Pasto [G. Z., J. L. R.], Colombia
Helicobacter pylori infection is a known risk factor for gastric cancer. We hypothesized that H. pylori infection would lead to the sustained production of the reactive nitrogen species nitric oxide and peroxynitrite as part of the host immune response. We further hypothesized that H. pylori infection would lead to increased apoptosis of gastric epithelial cells, possibly in response to free radical-mediated DNA damage. Using immunohistochemistry, we stained and scored gastric antral biopsies from 84 Colombian patients with nonatrophic gastritis before and after treatment for H. pylori infection. We examined expression of inducible nitric oxide synthase (iNOS); nitrotyrosine, a marker for peroxynitrite; and DNA fragmentation, a marker for apoptosis. Patients were treated with triple therapy (amoxicillin, 500 mg three times a day for 2 weeks; metronidazole, 400 mg three times a day for 2 weeks; and bismuth subsalicylate, 262 mg four times a day for 2 weeks, followed by 262 mg every day for 4–12 months). Eradication of H. pylori infection resulted in a significant reduction in iNOS and nitrotyrosine staining and a marginally significant reduction in apoptosis. Dietary supplementation with ß-carotene (30 mg every day for 4–12 months) resulted in a significant decrease in iNOS staining. Supplementation with ascorbic acid (1 g twice a day for 4–12 months) led to a significant reduction in nitrotyrosine staining. In patients supplemented with either ascorbic acid or ß-carotene, there was a trend toward a reduction in apoptosis, but this was not statistically significant. We conclude that H. pylori infection is accompanied by the formation of endogenous reactive nitrogen intermediates, which may contribute to DNA damage and apoptosis. In addition to antimicrobial therapy, dietary supplementation with ß-carotene and ascorbic acid may prevent the formation of these potential carcinogens.
1 This study was funded in part by Program Project PO1-CA28842 of the National Cancer Institute, NIH, USPHS.
2 These authors contributed equally to this article.
3 To whom requests for reprints should be addressed, at Department of Pathology, Louisiana State University Medical Center, 1901 Perdido Street, New Orleans, LA 70112.
Received 2/ 7/96. Accepted 5/10/96.
This article has been cited by other articles:
|
|
 |
|
  S.-Z. Ding, Y. Minohara, X. J. Fan, J. Wang, V. E. Reyes, J. Patel, B. Dirden-Kramer, I. Boldogh, P. B. Ernst, and S. E. Crowe Helicobacter pylori Infection Induces Oxidative Stress and Programmed Cell Death in Human Gastric Epithelial Cells Infect. Immun., August 1, 2007; 75(8): 4030 - 4039. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Das, G. Suarez, E. J. Beswick, J. C. Sierra, D. Y. Graham, and V. E. Reyes Expression of B7-H1 on Gastric Epithelial Cells: Its Potential Role in Regulating T Cells during Helicobacter pylori Infection. J. Immunol., March 1, 2006; 176(5): 3000 - 3009. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Durkin, A. P. Moran, and P. J. Hanson Apoptosis induction in gastric mucous cells in vitro: lesser potency of Helicobacter pylori than Escherichia coli lipopolysaccharide, but positive interaction with ibuprofen Innate Immunity, February 1, 2006; 12(1): 47 - 56. [Abstract] [PDF]
|
|
|
|
 |
|
 K T Nam, S-Y Oh, B Ahn, Y B Kim, D D Jang, K-H Yang, K-B Hahm, and D-Y Kim Decreased Helicobacter pylori associated gastric carcinogenesis in mice lacking inducible nitric oxide synthase Gut, September 1, 2004; 53(9): 1250 - 1255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M H L P Souza, H. P. Lemos, R B Oliveira, and F Q Cunha Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice Gut, June 1, 2004; 53(6): 791 - 796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Parker, J. R. Cerhan, C. F. Lynch, B. C. Leibovich, and K. P. Cantor History of Urinary Tract Infection and Risk of Renal Cell Carcinoma Am. J. Epidemiol., January 1, 2004; 159(1): 42 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Willhite, T. L. Cover, and S. R. Blanke Cellular Vacuolation and Mitochondrial Cytochrome c Release Are Independent Outcomes of Helicobacter pylori Vacuolating Cytotoxin Activity That Are Each Dependent on Membrane Channel Formation J. Biol. Chem., November 28, 2003; 278(48): 48204 - 48209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Potoka, J. S. Upperman, X.-R. Zhang, J. R. Kaplan, S. J. Corey, A. Grishin, R. Zamora, and H. R. Ford Peroxynitrite inhibits enterocyte proliferation and modulates Src kinase activity in vitro Am J Physiol Gastrointest Liver Physiol, November 1, 2003; 285(5): G861 - G869. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. De Luca, A. Baldi, P. Russo, A. Todisco, L. Altucci, N. Giardullo, L. Pasquale, S. Iaquinto, V. D'Onofrio, M. C. Parodi, et al. Coexpression of Helicobacter Pylori's Proteins CagA and HspB Induces Cell Proliferation in AGS Gastric Epithelial Cells, Independently from the Bacterial Infection Cancer Res., October 1, 2003; 63(19): 6350 - 6356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Eguchi, N. Herschenhous, N. Kuzushita, and S. F. Moss Helicobacter pylori Increases Proteasome-mediated Degradation of p27kip1 in Gastric Epithelial Cells Cancer Res., August 1, 2003; 63(15): 4739 - 4746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N C T van Grieken, G A Meijer, A zur Hausen, S G M Meuwissen, J P A Baak, and E J Kuipers Increased apoptosis in gastric mucosa adjacent to intestinal metaplasia J. Clin. Pathol., May 1, 2003; 56(5): 358 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Correa Bacterial Infections as a Cause of Cancer J Natl Cancer Inst, April 2, 2003; 95(7): E3 - E3. [Full Text]
|
|
|
|
|
|
T. L. Cover, U. S. Krishna, D. A. Israel, and R. M. Peek Jr. Induction of Gastric Epithelial Cell Apoptosis by Helicobacter pylori Vacuolating Cytotoxin Cancer Res., March 1, 2003; 63(5): 951 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y Yang, C S Deng, J Z Peng, B C-Y Wong, S K Lam, and H H-X Xia Effect of Helicobacter pylori on apoptosis and apoptosis related genes in gastric cancer cells Mol. Pathol., February 1, 2003; 56(1): 19 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Yu, W K Leung, M Y Y Go, M C W Chan, K F To, E K W Ng, F K L Chan, T K W Ling, S C S Chung, and J J Y Sung Relationship between Helicobacter pylori babA2 status with gastric epithelial cell turnover and premalignant gastric lesions Gut, October 1, 2002; 51(4): 480 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Maeda, H Yoshida, Y Mitsuno, Y Hirata, K Ogura, Y Shiratori, and M Omata Analysis of apoptotic and antiapoptotic signalling pathways induced by Helicobacter pylori Mol. Pathol., October 1, 2002; 55(5): 286 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Suzuki, A. Yanaka, T. Shibahara, H. Matsui, A. Nakahara, N. Tanaka, H. Muto, T. Momoi, and Y. Uchiyama Ammonia-induced apoptosis is accelerated at higher pH in gastric surface mucous cells Am J Physiol Gastrointest Liver Physiol, October 1, 2002; 283(4): G986 - G995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. S. Lehmann, L. Terracciano, I. Carena, C. Baeriswyl, J. Drewe, L. Tornillo, G. De Libero, and C. Beglinger In situ correlation of cytokine secretion and apoptosis in Helicobacter pylori-associated gastritis Am J Physiol Gastrointest Liver Physiol, August 1, 2002; 283(2): G481 - G488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Gobert, B. D. Mersey, Y. Cheng, D. R. Blumberg, J. C. Newton, and K. T. Wilson Cutting Edge: Urease Release by Helicobacter pylori Stimulates Macrophage Inducible Nitric Oxide Synthase J. Immunol., June 15, 2002; 168(12): 6002 - 6006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Maeda, H Yoshida, Y Mitsuno, Y Hirata, K Ogura, Y Shiratori, and M Omata Analysis of apoptotic and antiapoptotic signalling pathways induced by Helicobacter pylori Gut, June 1, 2002; 50(6): 771 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Jones, A. S. Day, H. Jennings, P. T. Shannon, E. Galindo-Mata, and P. M. Sherman Enhanced Disease Severity in Helicobacter pylori-Infected Mice Deficient in Fas Signaling Infect. Immun., May 1, 2002; 70(5): 2591 - 2597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ando, R. M. Peek Jr., Y.-C. Lee, U. Krishna, K. Kusugami, and M. J. Blaser Host Cell Responses to Genotypically Similar Helicobacter pylori Isolates from United States and Japan Clin. Vaccine Immunol., January 1, 2002; 9(1): 167 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Jacobs, C. J. Connell, M. L. McCullough, A. Chao, C. R. Jonas, C. Rodriguez, E. E. Calle, and M. J. Thun Vitamin C, Vitamin E, and Multivitamin Supplement Use and Stomach Cancer Mortality in the Cancer Prevention Study II Cohort Cancer Epidemiol. Biomarkers Prev., January 1, 2002; 11(1): 35 - 41. [Abstract] [Full Text]
|
|
|
|
|
|
M. Jaiswal, N. F. LaRusso, and G. J. Gores Nitric oxide in gastrointestinal epithelial cell carcinogenesis: linking inflammation to oncogenesis Am J Physiol Gastrointest Liver Physiol, September 1, 2001; 281(3): G626 - G634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kawahara, S. Teshima, Y. Kuwano, A. Oka, K. Kishi, and K. Rokutan Helicobacter pylori lipopolysaccharide induces apoptosis of cultured guinea pig gastric mucosal cells Am J Physiol Gastrointest Liver Physiol, September 1, 2001; 281(3): G726 - G734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. I. Kim, Y. C. Lee, K. H. Lee, J. H. Han, C. Y. Chon, Y. M. Moon, J. K. Kang, and I. S. Park Effects of Nonsteroidal Anti-Inflammatory Drugs on Helicobacter pylori-Infected Gastric Mucosae of Mice: Apoptosis, Cell Proliferation, and Inflammatory Activity Infect. Immun., August 1, 2001; 69(8): 5056 - 5063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kuck, B. Kolmerer, C. Iking-Konert, P. H. Krammer, W. Stremmel, and J. Rudi Vacuolating Cytotoxin of Helicobacter pylori Induces Apoptosis in the Human Gastric Epithelial Cell Line AGS Infect. Immun., August 1, 2001; 69(8): 5080 - 5087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. H. Shomer, C. A. Dangler, M. D. Schrenzel, M. T. Whary, S. Xu, Y. Feng, B. J. Paster, F. E. Dewhirst, and J. G. Fox Cholangiohepatitis and Inflammatory Bowel Disease Induced by a Novel Urease-Negative Helicobacter Species in A/J and Tac:ICR:Hascidf RF Mice Experimental Biology and Medicine, May 1, 2001; 226(5): 420 - 428. [Abstract] [Full Text]
|
|
|
|
|
|
S. F. Moss, E. M. Sordillo, A. M. Abdalla, V. Makarov, Z. Hanzely, G. I. Perez-Perez, M. J. Blaser, and P. R. Holt Increased Gastric Epithelial Cell Apoptosis Associated with Colonization with cagA+ Helicobacter pylori Strains Cancer Res., February 1, 2001; 61(4): 1406 - 1411. [Abstract] [Full Text]
|
|
|
|
|
|
X. Fan, H. Gunasena, Z. Cheng, R. Espejo, S. E. Crowe, P. B. Ernst, and V. E. Reyes Helicobacter pylori Urease Binds to Class II MHC on Gastric Epithelial Cells and Induces Their Apoptosis J. Immunol., August 15, 2000; 165(4): 1918 - 1924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kuwahara, Y. Miyamoto, T. Akaike, T. Kubota, T. Sawa, S. Okamoto, and H. Maeda Helicobacter pylori Urease Suppresses Bactericidal Activity of Peroxynitrite via Carbon Dioxide Production Infect. Immun., August 1, 2000; 68(8): 4378 - 4383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, X. Fan, C. Lindholm, M. Bennett, J. O'Connoll, F. Shanahan, E. G. Brooks, V. E. Reyes, and P. B. Ernst Helicobacter pylori Modulates Lymphoepithelial Cell Interactions Leading to Epithelial Cell Damage through Fas/Fas Ligand Interactions Infect. Immun., July 1, 2000; 68(7): 4303 - 4311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Alderman, G. A. Cook, M. Familari, N. D. Yeomans, and A. S. Giraud Resistance to apoptosis is a mechanism of adaptation of rat stomach to aspirin Am J Physiol Gastrointest Liver Physiol, June 1, 2000; 278(6): G839 - G846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Obst, S. Wagner, K.F. Sewing, and W. Beil Helicobacter pylori causes DNA damage in gastric epithelial cells Carcinogenesis, June 1, 2000; 21(6): 1111 - 1115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. MIZUKI, T. SHIMOYAMA, S. FUKUDA, Q. LIU, S. NAKAJI, and A. MUNAKATA Association of gastric epithelial apoptosis with the ability of Helicobacter pylori to induce a neutrophil oxidative burst J. Med. Microbiol., June 1, 2000; 49(6): 521 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C L Potter and P J Hanson Exogenous nitric oxide inhibits apoptosis in guinea pig gastric mucous cells Gut, February 1, 2000; 46(2): 156 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. K. Leung, J. J. Kim, J. G. Kim, D. Y. Graham, and A. R. Sepulveda Microsatellite Instability in Gastric Intestinal Metaplasia in Patients with and without Gastric Cancer Am. J. Pathol., February 1, 2000; 156(2): 537 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Aust and J. F. Eveleigh Mechanisms of DNA Oxidation Experimental Biology and Medicine, December 1, 1999; 222(3): 246 - 252. [Abstract] [Full Text]
|
|
|
|
|
|
R. M. Peek Jr., M. J. Blaser, D. J. Mays, M. H. Forsyth, T. L. Cover, S. Y. Song, U. Krishna, and J. A. Pietenpol Helicobacter pylori Strain-specific Genotypes and Modulation of the Gastric Epithelial Cell Cycle Cancer Res., December 1, 1999; 59(24): 6124 - 6131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. L. Jones, A. S. Day, H. A. Jennings, and P. M. Sherman Helicobacter pylori Induces Gastric Epithelial Cell Apoptosis in Association with Increased Fas Receptor Expression Infect. Immun., August 1, 1999; 67(8): 4237 - 4242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Shibata, H Goto, T Arisawa, Y Niwa, T Hayakawa, A Nakayama, and N Mori Regulation of tumour necrosis factor (TNF) induced apoptosis by soluble TNF receptors in Helicobacter pylori infection Gut, July 1, 1999; 45(1): 24 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C Carr and B. Frei Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans Am. J. Clinical Nutrition, June 1, 1999; 69(6): 1086 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. CARR and B. FREI Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J, June 1, 1999; 13(9): 1007 - 1024. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. Goto, K. Haruma, Y. Kitadai, M. Ito, M. Yoshihara, K. Sumii, N. Hayakawa, and G. Kajiyama Enhanced Expression of Inducible Nitric Oxide Synthase and Nitrotyrosine in Gastric Mucosa of Gastric Cancer Patients Clin. Cancer Res., June 1, 1999; 5(6): 1411 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Crane, S. Majumdar, and D. F. Pickhardt III Host Cell Death due to Enteropathogenic Escherichia coli Has Features of Apoptosis Infect. Immun., May 1, 1999; 67(5): 2575 - 2584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shirin, E. M. Sordillo, S. H. Oh, H. Yamamoto, T. Delohery, I. B. Weinstein, and S. F. Moss Helicobacter pylori Inhibits the G1 to S Transition in AGS Gastric Epithelial Cells Cancer Res., May 1, 1999; 59(10): 2277 - 2281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Minamoto, M. Mai, and Z.'e. Ronai Environmental factors as regulators and effectors of multistep carcinogenesis Carcinogenesis, April 1, 1999; 20(4): 519 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. S. Miller and M. Sandoval III. A molecular prelude to intestinal inflammation Am J Physiol Gastrointest Liver Physiol, April 1, 1999; 276(4): G795 - G799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gong, R. Mera, J. C. Bravo, B. Ruiz, R. Diaz-Escamilla, E. T. H. Fontham, P. Correa, and J. D. Hunt KRAS Mutations Predict Progression of Preneoplastic Gastric Lesions Cancer Epidemiol. Biomarkers Prev., February 1, 1999; 8(2): 167 - 171. [Abstract] [Full Text]
|
|
|
|
|
|
H SHIRIN and S F MOSS Helicobacter pylori induced apoptosis Gut, November 1, 1998; 43(5): 592 - 594. [Full Text] [PDF]
|
|
|
|
|
|
M. Romano, V. Ricci, A. Memoli, C. Tuccillo, A. Di Popolo, P. Sommi, A. M. Acquaviva, C. D. V. Blanco, C. B. Bruni, and R. Zarrilli Helicobacter pylori Up-regulates Cyclooxygenase-2 mRNA Expression and Prostaglandin E2 Synthesis in MKN 28 Gastric Mucosal Cells in Vitro J. Biol. Chem., October 30, 1998; 273(44): 28560 - 28563. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Pfeiffer and B. Mayer Lack of Tyrosine Nitration by Peroxynitrite Generated at Physiological pH J. Biol. Chem., October 16, 1998; 273(42): 27280 - 27285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Fan, S. E. Crowe, S. Behar, H. Gunasena, G. Ye, H. Haeberle, N. Van Houten, W. K. Gourley, P. B. Ernst, and V. E. Reyes The Effect of Class II Major Histocompatibility Complex Expression on Adherence of Helicobacter pylori and Induction of Apoptosis in Gastric Epithelial Cells: A Mechanism for T Helper Cell Type 1-mediated Damage J. Exp. Med., May 18, 1998; 187(10): 1659 - 1669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-T. Lin, J.-Y. Xue, M. C. Lin, E. G. Spokas, F. F. Sun, and P. Y.-K. Wong Peroxynitrite induces apoptosis of HL-60 cells by activation of a caspase-3 family protease Am J Physiol Cell Physiol, April 1, 1998; 274(4): C855 - C860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Zhuang and G. N. Wogan Growth and viability of macrophages continuously stimulated to produce nitric oxide PNAS, October 28, 1997; 94(22): 11875 - 11880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bouton, H. Hirling, and J.-C. Drapier Redox Modulation of Iron Regulatory Proteins by Peroxynitrite J. Biol. Chem., August 8, 1997; 272(32): 19969 - 19975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Gunther, L. C. Hsi, J. F. Curtis, J. K. Gierse, L. J. Marnett, T. E. Eling, and R. P. Mason Nitric Oxide Trapping of the Tyrosyl Radical of Prostaglandin H Synthase-2 Leads to Tyrosine Iminoxyl Radical and Nitrotyrosine Formation J. Biol. Chem., July 4, 1997; 272(27): 17086 - 17090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Moshage Nitric Oxide Determinations: Much Ado About NO•-Thing? Clin. Chem., April 1, 1997; 43(4): 553 - 556. [Full Text] [PDF]
|
|
|
|
|
|
A. Gal and G. N. Wogan Mutagenesis associated with nitric oxide production in transgenic SJL mice PNAS, December 24, 1996; 93(26): 15102 - 15107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Gupta, D. B. Polk, U. Krishna, D. A. Israel, F. Yan, R. N. DuBois, and R. M. Peek Jr. Activation of Peroxisome Proliferator-activated Receptor gamma Suppresses Nuclear Factor kappa B-mediated Apoptosis Induced by Helicobacter pylori in Gastric Epithelial Cells J. Biol. Chem., August 10, 2001; 276(33): 31059 - 31066. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS |
