The impact of sodium nitrite on carcinogenesis induced by skin application of benzo(a)pyrene

Cover Page

Cite item

Full Text

Abstract

An important feature of the modern life is a significant environmental pollution, which creates the danger of simultaneous effects of carcinogenic and toxic compounds on the human organism. The combined effect of such ubiquitously common compounds as benzo(a)pyrene (BP) and nitrites (NI) was studied in the experiment, on 320 female mice F1 (CBAxC57BL/6). The mice (6 groups of 50 animals) received BP application on the skin at a dose of 6 or 9 µg/mouse (two cycles for 12 weeks each) or BP in the same doses in combination with sodium nitrite (SN) was administered to animals with water at a concentration of 50 mg/l or 500 mg/l throughout the entire experiment. The study revealed SN to have moderate potent effects on carcinogenesis induced by cutaneous application of BP, increasing tumor multiplicity index by 1.4–1.6 times (p < 0,05), as well as the prevalence rate of skin tumors and hormone-dependent tumors. Under the action of the maximum doses of BP + SN (9 µg + 500 mg/l), the number of animals with skin tumors increased by 2.4 times (p < 0.01). The number of animals with hormone-dependent tumors (total: breast, ovary, and uterus) increased by 2.8–3.5 times (p < 0.01) under the combined effect on BP+SN compared with that of BP alone. There is discussed a possible mechanism of the stimulation the carcinogenic process due to the increased appearance of reactive oxygen species, nitric oxide metabolites, as well as the suppression of the phagocytic function of blood neutrophils.

About the authors

N. I. Ryzhova

N.N. Blokhin Russian Cancer Research Center

Author for correspondence.
Email: noemail@neicon.ru
Russian Federation

Valentina P. Deryagina

N.N. Blokhin Russian Cancer Research Center

Email: derygina@inbox.ru

MD, Ph.D., senior researcher of the Institute of Carcinogenesis of the N.N. Blokhin Russian Cancer Research Center, Moscow, 115478, Russian Federation.

e-mail: derygina@inbox.ru

Russian Federation

A. P. Ilnitsky

N.N. Blokhin Russian Cancer Research Center

Email: noemail@neicon.ru
Russian Federation

References

  1. IARC monographs on the evaluation of carcinogenic risks to humans. Chemical agents and related occupations. Benzo[a]pyrene. Lyon: IARC. 2012; 100F: 111-44.
  2. IARC monographs on the evaluation of carcinogenic risk to humans. Ingested nitrate and nitrite, and cyanobacterial peptide toxins. Lyon: IARC. 2010; 94: 45-325.
  3. Opopol’ M.I., Dobryanskaya E.V. Nitrates. Kishenev: Shtiinca; 1986: 113. (In Russian).
  4. Thomas D.D., Ridnour L.A., Isenberg J.S., Flores-Santana W., Switzer Ch. H., Donzellie S. et al. The Chemical biology of nitric oxide. Implication in Cellular Signaling. Free Radical Biol. Med. 2008; 45 (1): 18-31.
  5. Ilnitsky A.P. and Kolpakova A.S. The enhancing effect of sodium nitrite on virus-induced leukemia in mice. Cancer detection and prevention. 1997; 21 (4): 312-8.
  6. Ilnitsky A.P., Reutov V.P., Ryzhova N.I., Kolpakova A.S., Deryagina V.P., Nekrasova E.A., et al. Urethane-induced pulmonary adenoma and Rausherۥs leukemia modified by sodium nitrite in mice: a possible role for nitric oxide and nitric dioxide. Experemental oncology. 1997; 19: 101-9.
  7. Ilnitsky A.P., Ryzhova N.I., Chudina A.P., Nevzorova N.I., Nekrasova E.A. The enhancing effect of sodium nitrite on development of the spontaneous and induced by 1,2 dimethylhydrazine tumors in mice males of F1(C57BlxCBA). Voprosy onkologii. 2004; 50 (6): 683-8 (in Russian).
  8. Ilnitsky A.P., Andrianov A.P., Kolpakova A.S., Knyazev D.K., Shcherbak N.P. Sodium nitrite as a modifier blastomatosis. Vestnik ONTs RAMN. 1993; Prilozhenie 1: 13-8. (in Russian).
  9. Berezhnaya N.M., Chekhun V.F. Immunology of malignant growth. Kiev: Naukova dumka; 2005. (in Russian).
  10. Potselueva M.M., Pustovidko A.V., Kovaleva E.V., Shatalin Iu.V., Evdotienko Iu.V. Cytotoxic action of polymorphonuclear leukocytes on tumor and normal cells during ascite tumor development in vitro and in vivo. Tsitologiia. 2005; 47 (1): 57-63. (in Russian).
  11. Beda N.V., Nedospasov A.A. NO dependent modifications of nucleinic acids. Bioorganicheskaya himiya. 2007; 33 (2): 195-228 (in Russian).
  12. Muntane J. and De la Mata M. Nitric oxide and cancer. World J. Hepatol. 2010; 2(9): 337-44.
  13. Choudhari Sh.K., Chaudhary M., Bagde S., Gadbail A.R. and Joshi V. Nitric oxide and cancer: a review. Word J. Oncol. 2013; 11: 118.
  14. Merkulov G.A. Course pathological techniques. Moskva: Medicina; 1969. (in Russian).
  15. Turusov V.S. Pathology of tumors in laboratory animal. Tumors in the mouse. In IARC. Lyon; 1979: 655.
  16. Haitov R.M., Pinegin B.V., Istamov H.I. Ecological immunology. M.: VNIRO; 1995. (In Russian).
  17. Deryagina V.P., Mashkovtsev Yu.V., Ilnitsky A.P. Experimental study of functional activity neutrophiles and macrophages followed effect produced by sodium nitrite. Biomedicinskaya himiya. 2003; 49 (1): 19-26. (In Russian).
  18. Cortas N.K., Wakid N.W. Pharmacokinetic aspects of inorganic nitrate ingestion in man. Pharmacol Toxicol. 1991; 68 (3): 192-5.
  19. Tsikas D. Analysis of nitrite and nitrate in biological fluids by assay based on the Griess reaction: Appraisal of the Griess reaction in the L-arginine/nitric oxide area of research. J. Chromatog. 2007; 851: 51-70.
  20. Gubler E.V. Computing methods of the analysis and recognition of pathological processes. Moskva: Medicina; 1978. (in Russian)
  21. Krasnova T.A., Klepikov N.N., Kharkovskaya N.A., Schevyakova L.Ya, Khrustalev S.A. Oncoligical and genetic characterization of first generation hybrid mice (CBAxC57BL/6)F1. Vestnik rossijskogo onkologicheskogo centra imeni N.N. Blohina. 2005; 1-2: 3-6. (in Russian)
  22. Yurchenko V.A., Linnik A.B., Ilnitsky A.P. Carcinogenic risk of low doses of nitrite due to the endogenous synthesis of nitroso compounds. Eksperimentalnaya onkologiya. 1986; 1: 41-3. (in Russian)
  23. Savitskiy I.V. The pathophysiological mechanisms of participation of nitric oxide in the formation ekozavisimoy pathology of the reproductive system: diss. Moskow; 2003 (in Russian).
  24. Osinkovskaya N.D. Evaluation of the damaging and transforming action of sodium nitrite on lung cells in culture. Eksperimentalnaya onkologiya. 1987; 9 (6): 37-9. (n Russian).
  25. Sushko S.N., Malenchenko A.F. Induction of chromosomal aberrations in spermatocytes of mice. Radiobiologiy. 1992; 32 (4): 500-5. (in Russian)
  26. Mitchenkov V.T. Toxicological and hygienic evaluation of nitrate-nitrite loads on the human body and methodical bases its prevention: diss. Moskow; 1992. (in Russian).
  27. Deryagina V.P. Formation of free radical compounds under the influence of the sodium nitrite on animals’ organism and in vitro conditions. Toksikologicheskiy vestnik. 2003; (6): 20-5. (in Russian).
  28. Stepuro I. I., Chaykovskaya N. A., Solodunov A. A., Artsukevich A. N. NO formation in the process of nitrite oxidation of hemoglobin ferroforms. Biohimiya. 1997; 62 (9): 1122-9. (in Russian).
  29. Reutov V.P., Sorokina E. G., Okhotin V. E., Kositsin N. S. Cyclic nitrogen oxide transformations in the organism of mammals. Moskva: Nauka; 1997. (in Russian).
  30. Cheng H., Wang L., Mollica M., Re A.T., Wu Sh. and Zuo L. Nitric oxide in cancer metastasis. Cancer Lett. 2014; 353 (1): 1-7.
  31. Bonavida B. Nitric oxide-mediated sensitization of resistant tumor cells to apoptosis by chemo-immunotherapeutics. Redox biology. 2015; 6: 486-94.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Ryzhova N.I., Deryagina V.P., Ilnitsky A.P.


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 37884 от 02.10.2009.