Skip to main content

Helicobacter pylori infection can modulate the susceptibility of gastric mucosa cells to MNNG


The pathogenesis of stomach cells can be associated with their susceptibility to exogenous dietary irritants, like nitrosamines such as dimethylnitrosamines (DMNA), and to the effects of non-dietary factors, including Helicobacter pylori infection. We used N-methyl-N’-nitro N-nitrosoguanidyne (MNNG) as a surrogate agent that induces a spectrum of DNA damage similar to DMNA. Using the alkaline comet assay, we showed that antioxidants — vitamins C and E, quercetin, and melatonin — reduced the genotoxic effect of MNNG in H. pylori-infected and non-infected human gastric mucosa cells (GMCs). To compare the sensitivity of the stomach and the blood, the experiment was also carried out in peripheral blood. We observed a higher level of DNA damage induced by MNNG in H. pylori-infected than in noninfected GMCs. We did not note any difference in the efficacy of the repair of the damage in either type of GMC. H. pylori infection may play an important role in the pathogenesis of GMCs, as it can modulate their susceptibility to dietary mutagens/carcinogens, thus contributing to gastric cancer.



gastric mucosa cells




peripherial blood lymphocytes


  1. Yamaguchi, N. and Kakizoe, T. Synergistic interaction between Helicobacter pylori gastritis and diet in gastric cancer. Lancet 2 (2001) 84–94.

    Google Scholar 

  2. Zatomski, W., Oshima, H. and Przewoźniak, K. Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high-and low risk areas for stomach cancer in Poland. Int. J. Cancer 44 (1989) 823–827.

    Google Scholar 

  3. Mannick, E.E., Bravo, L.E., Zarama, G., Realpe, J.L., Zhang, X.J., Ruiz, B., Fontham, E.T., Mera, R., Miller, M.J. and Correa, P. Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants. Cancer Res. 56 (1996) 3238–3243.

    PubMed  CAS  Google Scholar 

  4. Parsonnet, J., Friedmann, G.D., Vandersteen, D.P., Chang, Y., Vogelman, J., Orentreich, N. and Sibley, R.K. Helicobacter pylori infection and the risk of gastric carcinoma. N. Engl. J. Med. 325 (1991) 1127–1131.

    Article  PubMed  CAS  Google Scholar 

  5. Eurogast Study Group. An international association between Helicobacter pylori infection and gastric cancer. Lancet 341 (1993) 1359–1362s.

    Article  Google Scholar 

  6. De Luca, A. and Iaquinto, G. Helicobacter pylori and gastric diseases: a dangerous association. Cancer Lett. 213 (2004) 1–10.

    Article  PubMed  CAS  Google Scholar 

  7. Blasiak, J., Trzeciak, A., Gasiorowska, A., Drzewoski, J. and Malecka-Panas, E. Vitamin C and quercetin modulate DNA-damaging effect of N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). Plant Foods Hum. Nutr. 57 (2002) 53–61.

    Article  PubMed  CAS  Google Scholar 

  8. Singh, N.P., McKoy, M.T., Tice, R.R. and Schneider, E.L. A simple technique for quanitation of low levels of damage in individual cells. Exp. Cell Res. 175 (1988) 184–191.

    Article  PubMed  CAS  Google Scholar 

  9. Arabski, M., Kazmierczak, P., Wisniewska-Jarosinska, P., Poplawski, T., Klupinska, G., Chojnacki, J., Drzewoski, J. and Blasiak, J. Interaction of amoxicillin with DNA in human lymphocytes and H. pylori-infected and non-infected gastric mucosa cells. Chem-Biol. Interact. 152 (2005) 13–24.

    Article  PubMed  CAS  Google Scholar 

  10. Bignami, M., O’Driscoll, M., Aquilina, G. and Karran, P. Unmasking a killer: DNA O(6)-methylguanine and the cytotoxicity of methylating agents. Mutat. Res. 462 (2000) 71–82.

    Article  PubMed  CAS  Google Scholar 

  11. Arabski, M., Klupinska, G., Chojnacki, J., Kazmierczak, P., Wisniewska-Jarosinska, M., Drzewoski, J. and Blasiak, J. DNA damage and repair in Helicobacter pylori-infected gastric mucosa cells. Mutat. Res. 570 (2005) 129–135.

    PubMed  CAS  Google Scholar 

  12. Kimura, N. and Miwa, T. Immunocytochemical and biochemical studies of glutathione-peroxidase (GSH-PO) in rat gastric parietal cells. Acta Histochem. Cytochem. 35 (2002) 23–31.

    Article  CAS  Google Scholar 

  13. Figura, N. Helicobacter pylori factors involved in the development of gastroduodenal mucosal damage and ulceration. J. Clin. Gastroenterol. 1 (1997) 149–163.

    Article  Google Scholar 

  14. Reiter, R.J., Tan, D.X., Manchester, L.C. and Qi, W. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species. Cell Biochem. Biophys. 34 (2001) 237–256.

    Article  PubMed  CAS  Google Scholar 

  15. Liu, J., Li, X., Yue, Y., Li, J., He, T. and He, Y. The inhibitory effect of quercetin on IL-6 production by LPS-stimulated neutrophils. Cell Mol. Immunol. 2 (2005) 455–460.

    PubMed  CAS  Google Scholar 

  16. Kempuraj, D., Madhappan, B., Christodoulou, S., Boucher, W., Cao, J., Papadopoulou, N., Cetrulo, C.L. and Theoharides, T.C. Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells. Br. J. Pharmacol. 145 (2005) 934–944.

    Article  PubMed  CAS  Google Scholar 

  17. Everett, S.M., Drake, I.M., White, K.L.M., Mapstone, N.P., Chalmers, D.M., Schorah, J. and Axon, A.T.R. Antioxidant vitamin supplement do not reduce reactive oxygen species activity in Helicobacter pylori gastritis in the short term. Br. J. Nutr. 87 (2002) 3–11.

    Article  PubMed  CAS  Google Scholar 

  18. Honig, A., Witte, F., Mirecka, J., Binder, C. and Schauer, A. Helicobacter pylori-induced hyperproliferation: relevance for gastric cancer development in connection with mutagenic factors. Anticancer Res. 20 (2000) 1641–1648.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Janusz Błasiak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arabski, M., Kazmierczak, P., Wiśniewska-Jarosińska, M. et al. Helicobacter pylori infection can modulate the susceptibility of gastric mucosa cells to MNNG. Cell Mol Biol Lett 11, 570–578 (2006).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Key words