JCT  Vol.2 No.5 , December 2011
Role of Nitrite in Tumor Growth, Symbiogenetic Evolution of Cancer Cells, and China’s Successes in the War against Cancer
Abstract: Statistics and experiments indicate a correlation between cancer mortality and nitrite in drinking water. Nitrite is a reductant that can deprive a cell of oxygen; it is also an oxidant that can be a substrate in anaerobic ammonium oxidation, the metabolic mode of the anammox bacteria. Eukaryote cells evolved through a fusion of anaerobic and aerobic bacteria. We postulate that an anammox bacterium sought refuge in a fusion with a membrane-bound cluster of aerobic bacteria. While the latter evolved into mitochondria organelles, the former became the nucleus of a prokaryote cell. Eventually, oxidative phosphorilation is the characteristic metabolic pathway of normal eukaryote cells, and we postulate that anammox is the protein-catabolism pathway for cancer cells. The metabolism consumes nitrite and explains thus the link between nitrite and cancer.
Cite this paper: nullK. Hsu, C. Huangfu and M. Qin, "Role of Nitrite in Tumor Growth, Symbiogenetic Evolution of Cancer Cells, and China’s Successes in the War against Cancer," Journal of Cancer Therapy, Vol. 2 No. 5, 2011, pp. 601-606. doi: 10.4236/jct.2011.25080.

[1]   National Academy of Sciences, National Research Council, Life Sciences Council, “The Health effect of Nitrate, Nitrite and N-Nitroso,” National Academy Press, Washington DC, 1981.

[2]   Committee of Experts on Health Control of Foodstuffs, “Nitrates and Nitrites in Foodstuffs,” Council of Europe Press, Strasbourg, 1993, p. 128.

[3]   D. C. Paik, D. V. Saborio, R. Oropeza and H. P. Freeman, “The Epidemiological Enigma of Gastric Cancer Rates in the US,” International Journal of Epidemiology, Vol. 30, No. 1, 2001, pp. 181-182. doi:10.1093/ije/30.1.181

[4]   Y. Kitamura, T. Umemura, K. Okazaki, et al., “Enhancing Effects of Simultaneous Treatment with Sodium Nitrite on 2-Amino-3-methylimidazo[4,5-f] Quinoline-Induced Rat Liver, Colon and Zymbal’s Gland Carcinogenesis after Initiation with Diethylnitrosamine and 1,2-Dimethylhydrazine,” International Journal of Cancer, Vol. 118, No. 10, 2006, pp. 2399-2404. doi:10.1002/ijc.21649

[5]   T. H. Tseng, M. C. Chang, J. D. Hsu, et al., “Tumor Promoting Effect of N-nitroso-N-(2-hexanonyl)-3’-nitrotyramine (a Nitrosated Maillard Reaction Product) in Benzoa Pyrene-Initiated Mouse Skin Carcinogenesis,” Chemico-Biological Interactions, Vol. 115, No. 1, 1998, pp. 23-38. doi:10.1016/S0009-2797(98)00056-8

[6]   H. Tsuda and M. Hasegawa, “Malignant Transformation of Mouse BALB/c3T3 Cells Induced by NaNO2,” Carcinogenesis, Vol. 11, No. 4, 1990, pp. 595-597. doi:10.1093/carcin/11.4.595

[7]   J. Sun, K. Aoki, W. Wang, et al., “Sodium Nitrite-Induced Cytotoxicity in Cultured Human Gastric Epithelial Cells,” Toxicology in Vitro, Vol. 20, 2006, pp. 1133-1138. doi:10.1016/j.tiv.2006.02.005

[8]   O. I. Bol’shakova, A. G. Sverdlov and S. I. Timoshenko, “Effect of Nitric Oxide Donor on the Stability of Non-Transformed and Malignant Cells to Ultraviolet and Gamma Radiation,” Tsitologia, Vol. 46, 2004, pp. 39-42.

[9]   I. V. Kondakova, G. V. Zagrebel’naya and E. T. Choinzonov, “NO-Generating Compounds Modify Tumoritoxic Effect of Doxorubicin,” Bulletin of Experimental Biology and Medicine, Vol. 137, No. 6, 2004, pp. 585-587. doi:10.1023/B:BEBM.0000042719.10494.3f

[10]   A. Yoshida, T. Harada and T. Kitazawa, “Effects of Age on Endometrial Carcinogenesis Induced by Concurrent Oral Administration of Ethylenethiourea and Sodium Nitrite in Mice,” Experimental and Toxicologic Pathology, Vol. 48, No. 4, 1996, pp. 289-298. doi:10.1016/S0940-2993(96)80021-2

[11]   C. S. Huangfu, K. J. Hsu, M. Z. Qin and T. S. Ma, “The Relationship between Nitrite and Cancer,” Journal of Henan University (Natural Science), Volume for 2009, 2009, pp. 1-5.

[12]   D. Lai, “Geostatistical Analysis of Chinese Cancer Mortality,” Journal of Data Science, Vol. 2, 2004, pp. 177-193.

[13]   Z. X. Xu, “Chemical Fertilizers, Sewage-Treatment and Aesophageal Cancer (in Chinese),” Scientific Publishers, Beijing, 2003, p. 257.

[14]   W. Q. Lu, C. L. Chen and W. Z. Li, “Link between Cancer and Drinking Water Quality in Areas of High and of Low Cancer-Incidence,” Cancer in China, Vol. 9, 2000, p. 227.

[15]   J. Y. Han, M. X. Wang and Y. Ma, “Cancer Mortality Rate and Nitrite in Drinking Water, Linzhou (Chinese with English Abstract),” Henan Disease Control Medicine, Vol. 11, 2000, pp. 65-69.

[16]   X. Deng, C. Q. Lin and Z. G. Gu “Cancer-Mortality Rate of Nitrite in Canton’s Drinking Water (Chinese with English abstract),” Physiological Science, Vol. 23, 2004, pp. 38-41.

[17]   J. Han, “The Effect of Switching the Source of Drinking Water on the Cancer the Source of Drinking Water on the Cancer-Mortality Rate of Linzhou,” Journal of Environment and Health (Beijing), Vol. 22, 2005, pp. 200-202.

[18]   O. Warburg, “On the Origin of Cancer Cells,” Science, Vol. 123, No. 3191, 1956, pp. 309-314. doi:10.1126/science.123.3191.309

[19]   K. Garber, “Energy Boost: The Warburg Effect Returns in a New Theory of Cancer,” Journal of National Cancer Institute, Vol. 94, 2004, pp. 1805-1806. doi:10.1093/jnci/96.24.1805

[20]   R. A. Gatenby and R. J. Gillies, “Why do Cancers Have High Aerobic Glycolysis,” Nature Reviews Cancer, Vol. 4, 2004, pp. 891-899. doi:10.1038/nrc1478

[21]   H. Kremer, “The Silent Revolution in Cancer and AIDS Medicine,” Xlibris Corporation, Zurich, Vol. 633, 2008, p. 71.

[22]   K. J. Hsu, P. Matsumoto, W. H. Ye, Y. Zhen, S. X. Lu, J. L. Li and S. Sun, “Nitrite in Drinking Water and Cancer,” Scientia Sinica, 2009, In Press.

[23]   A. Mulder, “Anoxic Ammonium Oxidation,” US Patent No. 427849, 1992.

[24]   A. Mulder, A. A. Graaf, L. Robertson and J. G. Kuenen, “Anaerobic Ammonium Oxidation Discovered in a Denitrifying Fluidized Bed Reactor,” FEMS Microbiology Ecology, Vol. 16, No. 3, 1995, pp. 177-184. doi:10.1111/j.1574-6941.1995.tb00281.x

[25]   J. G. Kuenen and M. S. M. Jetten, “Extraordinary Anaerobic Ammonium Oxidizing Bacteria,” American Society for Microbiology News, Vol. 67, No. 9, 2001, p.12.

[26]   K. Egli, J. R. van der Meer and H. Siegrist, “The Anammox Process for Nitrogen Removal from Waste Water,” EAWAG News, Zurich, Vol. 56, 2005, pp. 20-21.

[27]   L. van Niftrik, W. J. Geerts, E. G. van Humbel, R. J. Webb, J. A. Fuerst and M. Strous, “Linking Ultrastructure and Function in Four Genera of Anaerobic-Ammonium Oxidation Bacteria,” Journal of Bacteriology, Vol. 190, No. 2, 2008, pp. 708-717. doi:10.1128/JB.01449-07

[28]   M. G. Klotz, P. S. G. Chain, A. F. El Sheikh, L. R. Hauser, S. G. Hommes, F. W. Lariomer, S. A. Malfatti, J. M. Norton, A. T. Poret-Peterson, L. M. Vergez and B. B. Ward, “Complete Genome Sequence of Marine Chemolithoautotrphic Amm-OX Bacterium Nitrosococcus oceani,” Applied and Environmental Microbiology, Vol. 72, 2006, pp. 6299-6315. doi:10.1128/AEM.00463-06

[29]   Sagan and L. Margulis, “On the Origin of Mitosing Cells,” Journal of Theoretical Biology, Vol. 14, 1967, pp. 255-274.

[30]   N. Lane, “Power, Sex, Suicide: Mitochondria and the Meaning of Life,” Oxford University Press, Oxford, 2005, p. 354.

[31]   M. Kobayashi, Y. Matsuo, A. Takimoto, S. Suzuki, F. Maruo and H. Shoun, “De-Nitrification, a Novel Type of Respiratory Metabolism in Fungal Mitochondrion,” Journal of Chemical Biology, Vol. 271, No. 27, 1996, pp. 16263-16267. doi:10.1074/jbc.271.27.16263

[32]   M. Stoimenova, A. Igamberdiev, K. J. Gupta and R. D. Hill, “Nitrite-Driven Anaerobic ATP Synthesis in Barley and Rice Root Mitochondria,” Planta, Vol. 226, No. 2, 2007, pp. 465-474. doi:10.1007/s00425-007-0496-0

[33]   H. H. Mitchell, H. Shoule and H. S. Grindley, “The Origin of Nitrates in Urine,” Journal of Biological Chemistry, Vol. 24, 1916, pp. 461-490.

[34]   J. O. Lundberg, J. Weitzberg, J. A. Cole and N. Benjamine, “Nitrate, Bacteria and Human Health,” Nature Review/Microbiology, Vol. 2, 2004, pp. 593-602.

[35]   S. Ito, T. Kohli, H. Murakita, Y. Ohotaki, T. Azuma and M. Kruiyama, “Differences in Urease Activity in the Live Helicobacter pylori Cultured from Patients with Gastgroduodenal Diseases,” European Journal of Gastroenterology and Hepatology, Vol. 7, 1989, pp. 83-88.

[36]   B. Alternberg, C. Gemuend and K. O. Greulich, “Ubiquitous Cancer Genes: Multipurpose Molecules for Protein Micro-Arrays,” Proteomics, Vol. 6, 2007, pp. 67-71. doi:10.1002/pmic.200500154

[37]   C. H. Wu, M. Huang, C. S. Yeh, J. W. Wang, T. L. Cheng and S. R. Lin, “Over Expression of Helicobacter Pylori-Associated Urease mRNAs in Human Gastric Cancer,” DNA and Cell Biology, Vol. 2, 2007, pp. 641-648. doi:10.1089/dna.2007.0599

[38]   J. Wang, Harvard University, June 2007.

[39]   C. V. Dang, D. Dean and J. Hopkins, Medical School, June 2007.

[40]   K. J. Hsu, W. H. Ye, Y. H. Kong, D. Li and F. Hu, “Use of Hydrotransistor and Self-Cleaning Pond for De-Nitrification to Produce Purified Non-Carcinogenic Water for Drinking and for Groundwater Recharge,” Technical Report, Tarim Resources Recycling Ltd., Haslemere, 2007.