Advertisement

Medical Oncology and Tumor Pharmacotherapy

, Volume 8, Issue 4, pp 235–241 | Cite as

Analysis of some metabolic conditions promoting selective sensitivity of tumor cells to peroxidative stress

  • P. M. Schwartzburd
  • K. B. Aslanidi
Article
  • 17 Downloads

Abstract

Some metabolic parameters enhancing the sensitivity of tumor ceils and their iipoprotein refractive granules (RG) to peroxidative stress were investigated during the growth cycle of ascite tumorsin vivo. The majority of tumor cells only in the stationary growth phase had the increased sensitivity to peroxidative stress, tested by fluorescence intensivity of peroxidation products. The increase of this intensity correlates well with the decrease of tumor proliferation, the functional activity of mitochondria, the cellular level of ATP and extracellular pH. These metabolic conditions are favourable for increasing the neutral lipid accumulation in the stationary tumor cells, their RG and nuclei, as compared to exponentially growing cells. The sensitivity of tumor cells to peroxidation can be also enhanced with the help of exogenous polyunsaturated fatty acid (PUFA). Based on literature and our own data on Ehrlich ascites carcinoma (EAC), a working hypothesis is proposed to explain the enhanced selective sensitivity of tumor cells to PUFA peroxidation products (PP) suppressing the cell growth (especially in the stationary phase of EAC growth).

Key words

Tumor growth Selective suppression Lipoprotein granules Peroxidative stress Lipid peroxidation Polyunsaturated fatty acids 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cornwell D G, Morisak N: Fatty acid paradoxes in the control of cell proliferation: prostaglandins, lipid peroxides and cooxidation reactions, in Pryor W A (ed):Free Radicals in Biology., pp.95–136. Academic Press, London (1984).Google Scholar
  2. 2.
    Cerrutti P A: Oxidant tumor promoter, inGrowth Factors, Tumor Promoters, and Cancer Genes, 239–247. Alan R. Liss, New York (1988).Google Scholar
  3. 3.
    Cadenas E, Boviris A, Chance B: Low-level chemiluminescence of biological systems, in Pryor W A (ed):Free Radicals in Biology, 211–242. Academic Press, London (1984).Google Scholar
  4. 4.
    Begin M E, Das U N, Ells G, Horrobin D E: Selective killing of human cancer cells by polyunsaturated fatty adds.Prost Leukot Med 19, 177–186 (1985).CrossRefGoogle Scholar
  5. 5.
    Begin M E, Ells G, Horrobin D E: Polyunsaturated fatty acid induced cytotoxicity against tumor cells and its relationship to lipid peroxidation.J Nat Cancer Inst 80, 188–194 (1988).CrossRefPubMedGoogle Scholar
  6. 6.
    Das U N, Begin M E, Ells G, Huang Y S, Horrobin D F: Polyunsaturated fatty acids augment free radicals generation in tumor cellsin vitro.Biochem Biophys Res Commun 145, 15–24 (1987).CrossRefPubMedGoogle Scholar
  7. 7.
    Chow S C, Sisfontes L, Björkhem J, Jondal M: Suppression of growth in a leukemic T cell line by n-3 and n-6 polyunsaturated fatty acids.Lipids 24, 700–704 (1989).CrossRefPubMedGoogle Scholar
  8. 8.
    Fumihiro F, Shinjiro T, Shimsaki I: Fatty acid modification of cultured neuroblastoma cells by gamma linolenic acid relevant to its antitumor effect.Prostagland Leukot Med 30, 37–49 (1987).CrossRefGoogle Scholar
  9. 9.
    Masauoshi M S, Takahashi M D:Color Atlas of Cancer Cytology, 2ndEd. Springer, Stuttgart (1981).Google Scholar
  10. 10.
    Love R, Orsi E V, Koprowski H: Cytological and cytochemical properties of ten ascites tumors.J Biophys Biochem Cytol 2, 1–14 (1956).PubMedGoogle Scholar
  11. 11.
    Novikoff A B, Shin W Y, Drucker J: Localization of oxidative enzymes.Biochem Cytol 9, 61–73 (1961).Google Scholar
  12. 12.
    Shwartzburd P M: Cluster structures from lipid- containing granules in native Zaidela ascites cells, pp. 1–15. Academic Press, Pushchino, U.S.S.R. (1987).Google Scholar
  13. 13.
    Di Paolo J A, Heining A, Carruthers C: Isolation and lipid analysis of lipoid granules from Ehrlich ascites tumor cells.Proc Soc Exp Biol 113, 68–83 (1963).Google Scholar
  14. 14.
    Clark R W, Crain R C: Characterization of alterations in plasma lipoprotein lipid and apoprotein profiles accompanying hepatoma-induced hyperlipidemia in rats.Cancer Res 46, 1894–1903 (1986).PubMedGoogle Scholar
  15. 15.
    Spector A A, Brenneman D E: Role of free fatty acid and lipoproteins in the lipid nutrition of tumor cells, in Wood R (ed):Tumor Lipids. Biochemistry and Metabolism, 1–13. American Oil Chemists Society Press, Champaign, Illinois (1973).Google Scholar
  16. 16.
    Seki S, Oda T: DNA synthesis in permeable mouse ascites sarcoma cells.Cancer Res 37, 137–144 (1977).PubMedGoogle Scholar
  17. 17.
    Härnmerle T, Löffler M: Simultaneous analysis of mitochondrial activity and DNA content in Ehrlich ascites tumor cells by dual parameter flow cytometry.Histochemistry 93, 207–212 (1989).CrossRefGoogle Scholar
  18. 18.
    Taubert G, Krug H: Measurements with the interference microscope INTERPHAKO in biology and medicine.Jena Review 5, 218–226 (1972).Google Scholar
  19. 19.
    Schwartzburd P M, Aslanidi K B: Spectrokinetic characteristics of two types of fluorescence of refractive lipoprotein granules in native individual cells from ascitic tumors. Biomed Science (in press) (1991).Google Scholar
  20. 20.
    Schwartzburd P M, Aslanidi K B: Resistance of single tumor cells and their intracellular compartments to lipid peroxidation.Med Oncol & Tumor Pharmacother 8, 57–61 (1991).Google Scholar
  21. 21.
    Capel I D: Antioxidant defence in hypoxic regions of tumors.Med Biol 62, 119–121 (1984).PubMedGoogle Scholar
  22. 22.
    Dianzani M U, Canuto R A, Rossi M A, Biocca M E, Cecchini G, Biasi E, Ferro M, Bassi A M: Further experiments on lipid peroxidation in transplanted and experimental hepatomas.Toxicol Pathol 12, 189–199 (1984).PubMedCrossRefGoogle Scholar
  23. 23.
    Jamienson D: Reactive oxygen metabolites and hyperoxic toxicity, in Simic M G (ed): Oxygen radicals in biology and medicine, pp. 553–560. Plenum Press, New York (1988).Google Scholar
  24. 24.
    Deschner E E, Gray L H: Influence of oxygen tension of X-ray-induced chromosomal damage in Ehrlich ascites tumor cells irradiatedin vitro andin vivo.Rad Res 11, 115–146 (1959).CrossRefGoogle Scholar
  25. 25.
    Skog S, Ericsson A, Nordell B, Nishida T, Tribukait B: P-NMR-spectroscopy measurements of energy metabolism ofin vivo growing ascites tumours following addition of glucose.Ada Oncol 28, 277–281 (1989).CrossRefGoogle Scholar
  26. 26.
    Ide T, Ontko J A: Increased secretion of very low density lipoprotein triglyceride following inhibition of long chain fatty acid oxidation in isolated rat liver.J Biol Chem 256, 10247–10255 (1981).PubMedGoogle Scholar
  27. 27.
    Balint Z, Holczinger L: Lipid analysis of cell nuclei in young and old Ehrlich ascites tumors.Int J Cancer 14, 93–96 (1984).CrossRefGoogle Scholar
  28. 28.
    Balint Z: Lipids as integral constituents of nuclear and chromatin fractions in Ehrlich ascites tumor cells.Basic Appl Histochem 31, 365–376 (1987).PubMedGoogle Scholar
  29. 29.
    Lala P K, Patt H M: Cytokinetic analysis of tumor growth.Proc Nat Acad Sci 56, 1735–1742 (1966).CrossRefPubMedGoogle Scholar
  30. 30.
    Palmina N P, Malcheva E L: Nuclear neutral lipids for liver cells and Ehrlich ascites cells to tumor development.Report Acad Sci USSR 269, 1256–1259 (1983).Google Scholar
  31. 31.
    Zhu Y-P, Su Z-W, Li C-H: Growth-inhibition effects of oleic acid, linoleic acid and their methyl esters on transplanted tumors in mice.J Nat Cancer Inst 81, 1302–1306 (1989).CrossRefPubMedGoogle Scholar
  32. 32.
    Spector A A, Burn C P: Biological and therapeutic potential of membrane lipid modification in tumors47, 4529–4537 (1987).Google Scholar
  33. 33.
    Mackenzie C C, Mackenzie J B, Beck P: The effect of pH on growth, protein synthesis, and lipid-rich particles of cultured mammalian cells.J Biophys Biochem Cytology 9, 141–156 (1961).CrossRefGoogle Scholar
  34. 34.
    Spector A A: Influence of pH of the medium of free fatty acid utilization by isolated mammalian cells.J Lipid Res 10, 207–219 (1969).PubMedGoogle Scholar
  35. 35.
    Sukhorukov B I, Schwartzburd P M: Influence concentration H+ in environment on state of chromatin in lymphoid cells.Biophys 30, 637–641 (1985).Google Scholar
  36. 36.
    Van der Merwe C F: The reversibility of cancer.SA Med J 65, 712 (1984).Google Scholar

Copyright information

© Humana Press Inc. 1991

Authors and Affiliations

  • P. M. Schwartzburd
    • 1
  • K. B. Aslanidi
    • 1
  1. 1.Institute of Biological Physics, U.S.S.R. Academy of SciencesMoscow RegionU.S.S.R

Personalised recommendations