Applied Magnetic Resonance

, 2:495 | Cite as

ESR and31P NMR study of metabolic changes in mouse tumor and liver after combined misonidazole and irradiation treatment

  • Z. V. Kuropteva
  • V. E. Yushmanov
  • M. U. Jurczyk
  • D. S. Khristianovich
  • M. E. Kudryavtsev
  • L. A. Sibeldina
  • T. Pisarski


A combination of ESR and31P NMR techniques was used to study the mechanism of the radiosensitizing influence of misonidazole (MISO) on mouse tumors and liver. The MISO injection (1 g/kg) was shown to cause significant metabolic changes in tumors, such as an increase in the content of nitrosyl complexes, increases in adenosine diphosphate and inorganic phosphate levels, and decreases in phosphomonoesters, phosphodiesters, adenosine triphosphate and phosphocreatine in the initial period of observation. These alterations were accompanied by slight cytosol alkalinization (pH shift ca 0.15). A decrease in the ESR signal intensity of Mo5+-containing enzymes, an increase in the cytochrome P-450 signal and a significant increase in the free radical signal were observed in liver after MISO treatment. Local irradiation of tumors (30 Gy) 30 min after MISO injection led to the enhancement and prolongation of nearly all the effects induced by MISO treatment. The combined effect of MISO and irradiation was not simply the sum of their separate effects. It is suggested that radiation enhances cytotoxic effects of nitrocompounds on hypoxic tumor cells, inhibiting glycolysis and inducing greater production of toxic and highly reactive intermediates resulting from incomplete nitro group reduction. The latter appears to be considered as the major factor involved in the radiosensitizing action of nitrocompounds.


Electron Spin Resonance Electron Spin Resonance Spectrum Electron Spin Resonance Signal Nitrocompounds Liver Metabolism 
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  1. [1]
    Adams, G.E., Ahmed, I., Fielden, E.M., O’Neill, P., Stratford, I.J.: Cancer Clin. Trials3, 37–42 (1980)Google Scholar
  2. [2]
    Adams, G.E., Flockhart, I.R., Smithen, C.E., Stratford, I.J., Wardman, P., Watts, M.E.: Radiat. Res.67, 9–20 (1976)CrossRefGoogle Scholar
  3. [3]
    Hall, E.J., Roizen-Towle, L.: Radiology117, 453–457 (1975)Google Scholar
  4. [4]
    Moore, B.A., Palcic, B., Skarsgard, L.D.: Radiat. Res.67, 459–473 (1976)CrossRefGoogle Scholar
  5. [5]
    Biaglow, J.E., Varnes, M.E., Roizen-Towle, L., Clark, E.P., Epp, E.R., Astor, M.B., Hall, E.J.: Biochem. Pharmacol.35, 77–90 (1986)CrossRefGoogle Scholar
  6. [6]
    Brown, J.M.: Int. J. Radiat. Oncol. Biol. Phys.8, 675–682 (1982)Google Scholar
  7. [7]
    Wardman, P.: Radiat Phys. Chem.30, 423–432 (1987)Google Scholar
  8. [8]
    Edwards, D.I. in Progress in Medicinal Chemistry (Ellis, G.P., West, G.B., eds.), vol. 18, pp. 87–116. Amsterdam: Elsevier 1981.Google Scholar
  9. [9]
    Hofer, K.G., Friedland, J.L., Dynlacht, I., Hofer, M.G.: Radiat. Res.111, 130–142 (1987)CrossRefGoogle Scholar
  10. [10]
    Kuropteva, Z.V., Zhumabaeva, T.T.: Med. Radiol.31, 56–59 (1986) (in russian)Google Scholar
  11. [11]
    Taylor, Y.C., Evans, J.W., Brown, T.M.: Radiat. Res.109, 364–373 (1987)CrossRefGoogle Scholar
  12. [12]
    Zhumabaeva, T.T., Kudryavtsev, M.E., Voronina, S.S., Kuropteva, Z.V.: Radiobiologiya27, 384–389 (1987) (in russian)Google Scholar
  13. [13]
    Garlick, P.B., Radda, G.K., Seeley, P.J.: Biochem. J.184, 547–554 (1979)Google Scholar
  14. [14]
    Kuropteva, Z.V., Pastushenko, O.N.: Dokl. Akad. Nauk SSSR281, 189–192 (1985) (in russian)Google Scholar
  15. [15]
    Shubin, V.E., Kuropteva, Z.V.: Stud. Biophys.97, 157–165 (1983) (in russian)Google Scholar
  16. [16]
    Mason, R.P. in: Reviews in Biochemical Toxicology (Hodgson, E., Bend, J.R., and Philpot, R.M. eds.), pp. 151–200. Amsterdam: Elsevier 1979.Google Scholar
  17. [17]
    Hudges, M.N: The Inorganic Chemistry of Biological Processes, 2nd ed., pp. 172–177. Chichester: Wiley 1981.Google Scholar
  18. [18]
    Josephy, P.D., Palcic, B., Skarsgard, L.D.: Biochem. Pharmacol.30, 849–853 (1981)CrossRefGoogle Scholar
  19. [19]
    Wolpert, M.K., Althaus, J.R., Johns, D.G.: J. Pharmac. Exp. Ther.185, 202–213 (1973)Google Scholar
  20. [20]
    Kappus, H.: Biochem. Pharmacol.35, 1–6 (1986)CrossRefGoogle Scholar
  21. [21]
    Khristianovich, D.S., Mitrokhin, Yu.I., Yushmanov, V.E., Todorov, I.N., Sibeldina, L.A.: Biochemistry USSR (english translation)53, 1634–1638 (1988)Google Scholar
  22. [22]
    Yushmanov, V.E., Khristianovich, D.S., Sibeldina, L.A., Eichhoff, U.: Society of Magnetic Resonance in Medicine, 9th Annual Scientific Meeting. Abstracts, p. 1097. New York 1990.Google Scholar
  23. [23]
    Yushmanov, V.E., Mitrokhin, Yu.I., Shchelok, E.P., Todorov, I.N., Sibeldina, L.A.: Eksp. Onkol.11, N 6, 73 (1989) (in russian)Google Scholar
  24. [24]
    Jurczyk, M.U., Yushmanov, V.E., Khristianovich, D.S., Kudryavtsev, M.E., Kuropteva, Z.V., Sibeldina, L.A., Pisarski, T.: Stud. Biophys.133, 235–240 (1989)Google Scholar
  25. [25]
    Zhumabaeva, T.T., Shubin, V.E., Kuropteva, Z.V: Proceedings of the 3rd Meeting on Problems of Experimental Chemotherapy of Tumors, pp. 250–252. Chernogolovka, USSR 1987. (in russian)Google Scholar
  26. [26]
    McClelland, R.A., Fuller, J.R., Seaman, N.E., Rauth, A.M., Battistella, R.: Biochem. Pharmacol.33, 303–309 (1984)CrossRefGoogle Scholar
  27. [27]
    McClelland, R.A., Panicucci, R., Rauth, A.M.: J. Amer. Chem. Soc.109, 4308–4314 (1987)CrossRefGoogle Scholar
  28. [28]
    Varghese, A.J., Whitmore, G.F.: Chem. Biol. Interact.36, 141–151 (1981)CrossRefGoogle Scholar
  29. [29]
    Varghese, A.J., Whitmore, G.F.: Radiat. Res.97, 262–278 (1984)CrossRefGoogle Scholar
  30. [30]
    Whitmore, G.F., Gulyas, S., Varghese, A.J.: Br. J. Cancer37 (Suppl. III), 115–119 (1978)Google Scholar
  31. [31]
    Williams, D.W., Whitmore, G.F.: Radiat. Res.86, 311–324 (1981)CrossRefGoogle Scholar
  32. [32]
    Isichenko, T.S., Baider, L.M., Louchkov, V.B., Khleskov, V.I.: Koord. Khim., in press (1991) (in russian)Google Scholar
  33. [33]
    Isichenko, T.S., Louchkov, V.B.: Izv. Akad. Nauk SSSR, Ser. Khim., 1167–1169 (1989) (in russian)Google Scholar
  34. [34]
    Kuropteva, Z.V., Pulatova, M.K.: Symposium on Magnetic Resonance in Biology and Medicine, Moscow, USSR 1981, pp. 11–12. Chernogolovka 1981. (in russian)Google Scholar

Copyright information

© Springer 1991

Authors and Affiliations

  • Z. V. Kuropteva
    • 1
  • V. E. Yushmanov
    • 1
  • M. U. Jurczyk
    • 2
  • D. S. Khristianovich
    • 1
  • M. E. Kudryavtsev
    • 1
  • L. A. Sibeldina
    • 1
  • T. Pisarski
    • 2
  1. 1.Institute of Chemical Physics of the Academy of Sciences of the USSRMoscowUSSR
  2. 2.Institute of Obstetrics and GynecologyPoznanPoland

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