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Induction of Stress Proteins and Drug Resistance by Hypoxia and Applications of Magnetic Resonance Spectroscopy and Cryospectrophotometry for Detecting Hypoxia in Tumors

  • Chapter
Selective Activation of Drugs by Redox Processes

Part of the book series: NATO ASI Series ((NSSA,volume 198))

Abstract

Most malignant neoplasms are believed to be composed of heterogeneous populations of cells with a variety of phenotypic properties associated with different important malignancy traits1–3. Many of these phenotypes have been shown to be unstable, so that a tumor cell population may be a dynamic mixture of relatively stable and very transient phenotypes4,5. This steady-state population of cells may be perturbed by a variety of host-tumor factors as well as by therapeutic interventions6–8 The cause of this cellular heterogeneity has been considered traditionally to be due to increased genetic mutation frequencies associated with the inherent instability of the malignant phenotype4. However, more recently the possible importance of epigenetic factors has arisen9. Among such factors, one area which has received increased attention is the role of the different microenvironments within solid tumors that arise due to various pathophysiological factors related to growth of the cells and the inefficient vascular supply10,11.

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References

  1. A. H. Owens, D. S. Coffey, and S. B. Baylin (eds.), in: Tumor Cell Heterogeneity: Origins and Implications, Academic Press, New York (1982).

    Google Scholar 

  2. G. H. Heppner, Tumor heterogeneity, Cancer Res. 44:2259 (1984).

    PubMed  CAS  Google Scholar 

  3. I. J. Fidler and I. R. Hart, Biological diversity in metastatic neoplasms: origins and implications, Science 217:998 (1982).

    Article  PubMed  CAS  Google Scholar 

  4. P. C. Nowell, in: Tumor Cell Heterogeneity: Origins and Implications, A. Owens, D. S. Coffey, and S. B. Baylin (eds.), Academic Press, New York (1982).

    Google Scholar 

  5. R. P. Hill, A. F. Chambers, V. Ling, J. F. Harris, Dynamic heterogeneity: rapid generation of metastatic variants in mouse B16 melanoma cells, Science 224:998 (1984).

    Article  PubMed  CAS  Google Scholar 

  6. B. E. Miller, F. R. Miller, and G. H. Heppner, Interactions between tumor subpopulations affecting their sensitivity to the antineoplastic agents’ cyclophosphamide and methotrexate, Cancer Res. 41:4378 (1981).

    PubMed  CAS  Google Scholar 

  7. G. Poste and R. Greig, The genesis and regulation of cellular heterogeneity in malignant tumors, Invasion Metastasis 2:137 (1982).

    PubMed  CAS  Google Scholar 

  8. M. F. A. Woodruff, Interaction of cancer and host, Br. J. Cancer 46:313 (1982).

    Article  PubMed  CAS  Google Scholar 

  9. P. Frost and R. S. Kerbel, On a possible epigenetic mechanism(s) of tumor cell heterogeneity, The role of DNA methylation, Cancer Metastatis Rev. 2:375 (1984).

    Article  Google Scholar 

  10. P. M. Gullino, The internal milieu of tumors, Prog. Exp. Tumor Res. 8:1 (1966).

    CAS  Google Scholar 

  11. P. Vaupel, in: Tumor Blood Circulation: Angiogenesis, Morphology, and Blood Flow of Experimental and Human Tumors, H. E. Peterson (ed), CRC, Boca Raton (1984).

    Google Scholar 

  12. C. W. Song, Effect of local hyperthermia on blood flow and microenvironment: a review, Cancer Res. (Suppl.) 44:4721 (1984).

    Google Scholar 

  13. P. Wendung, R. Manz, G. Thews, and P. Vaupel, in: Oxygen Transport to Tissue — VI, D. Bruley, H. I. Bicher, and D. Renau (eds.), Plenum Press, New York (1985).

    Google Scholar 

  14. W. Mueller-Klieser, P. Vaupel, R. Manz, and R. Schmidseder, Intracapillary oxyhemoglobin saturation of malignant tumors in humans, Int. J. Radiat. Oncol. Biol. Phys. 7:1397 (1981).

    Article  PubMed  CAS  Google Scholar 

  15. J. E. Moulder and S. Rockwell, Hypoxic fractions of solid tumors: experimental techniques, methods of analysis, and a survey of existing data, Int. J. Radiat. Oncol. Biol. Phys. 10:695 (1984).

    Article  PubMed  CAS  Google Scholar 

  16. T. Nederman and P. Twentyman, in: Spheroids in Cancer Research: Methods and Perspectives, H. Acker, J. Carlsson, R. Curand, and R. Sutherland (eds.), Springer-Verlag, Berlin (1984).

    Google Scholar 

  17. L. E. Gerweck, Hyperthermia in cancer therapy: the biological basis and unresolved questions, Cancer Res. 45:3408 (1985).

    PubMed  CAS  Google Scholar 

  18. R. M. Sutherland, J. A. McCredie, and W. R. Inch, Growth of raulticell spheroids in tissue culture as a model of nodular carcinomas, J. Natl. Cancer Inst. 46:113–120 (1971).

    PubMed  CAS  Google Scholar 

  19. R. M. Sutherland and R. E. Durand, in: Spheroids in Cancer Research: Methods and Perspectives, H. Acker, J. Carlsson, R. Durand, and R. Sutherland (eds.), Springer-Verlag, Berlin (1984).

    Google Scholar 

  20. R. M. Sutherland, Cell and environment interaction in tumor microregions: The multicell spheroid model, Science 240:177–184 (1988).

    Article  PubMed  CAS  Google Scholar 

  21. J. P. Freyer and R. M. Sutherland, Selective dissociation and characterizations of cells from different regions of multicell tumor spheroids, Cancer Res. 40:3956–3965 (1981).

    Google Scholar 

  22. W. F. Mueller-Klieser and R. M. Sutherland, Oxygen tensions in multicell spheroids of two cell lines at different stages of growth, Br. J. Cancer 45:256–264 (1982).

    Article  PubMed  CAS  Google Scholar 

  23. A. J. Franko and C. J. Koch, Binding of misonidazole to V79 spheroids and fragments of Dunning rat prostatic and human colon carcinomas in vitro: diffusion of oxygen and reactive metabolites, Radiat. Res. 96:497 (1983).

    Article  PubMed  CAS  Google Scholar 

  24. R. M. Sutherland, H. A. Eddy, B. Bareham, D. Vanantwerp, and K. Reich, Resistance to adriamycin in multicellular spheroids, Int. J. Radiat. Oncol. Biol. Phys. 5:1225–1230 (1979).

    Article  PubMed  CAS  Google Scholar 

  25. C. K. Luk and R. M. Sutherland, Nutrient modification of proliferation and radiation response in EMT6/R0 spheroids, Int. J. Radiat. Oncol. Biol. Phys. 13:885–895 (1987).

    Article  PubMed  CAS  Google Scholar 

  26. L. Ling, C. Streffer, and R. Sutherland, Decreased hypoxic toxicity and binding of misonidazole by low glucose concentration, Int. J. Radiat. Oncol. Biol. Phys. 12:1231–1234 (1986).

    Article  PubMed  CAS  Google Scholar 

  27. R. E. Wilson and R. M. Sutherland, Enhanced synthesis of specific proteins, RNA, and DNA caused by hypoxia and reoxygenation, Int. J. Radiat. Oncol. Biol. Phys. 16:957 (1989).

    Article  PubMed  CAS  Google Scholar 

  28. E. Lazarides and B. L. Granger, Preparation and assay of the intermediate filament proteins desmin and vimentin, Methods in enzymology, New York Academic Press; 1982:488–508.

    Google Scholar 

  29. A. Brunsting, J. M. Collins, F. R. Kane, and C. B. Bagwell, An examination of some basic assumptions of DNA distribution analysis using biological data, Cell Tissue Kinetics 12:123–134 (1979).

    CAS  Google Scholar 

  30. C. K. Luk, P. C. Keng, and R. M. Sutherland, Regrowth and radiation sensitivity of quiescent cells isolated from EMT6/R0 fed plateau monolayers, Cancer Res. 45:1020 (1985).

    PubMed  CAS  Google Scholar 

  31. J. E. Thomson and A. M. Rauth, An in vitro assay to measure the viability of KHT tumor cells not previously exposed to culture conditions, Radiat. Res. 58:262 (1974).

    Article  PubMed  CAS  Google Scholar 

  32. P. R. Twentyman, J. M. Brown, J. W. Gray, A. J. Franko, M. A. Scoles, and R. F. Kallman, A new mouse tumor model system (RIF-1) for comparison of end-point studies, J. Natl. Cancer Inst. 64:595 (1980).

    PubMed  CAS  Google Scholar 

  33. E. K. Rofstad, P. De Muth, and R. M. Sutherland, 31P NMR spectroscopy measurements of human ovarian carcinoma xenografts: Relationship to tumour volume, growth rate, necrotic fraction and differentiation status, Radiother. Oncol. 12:315 (1988)

    Article  PubMed  CAS  Google Scholar 

  34. E. K. Rofstad, B. M. Fenton, and R. M. Sutherland, Intracapillary HbO2 saturations in murine tumour and human tumour xenografts measured by cryospectrophotometry: Relationships to tumour volume, tumour pH and fraction of radiobiologically hypoxic cells, Br. J. Cancer 57:494 (1980).

    Article  Google Scholar 

  35. T. E. J. Gayeski, A cryogenic microspectrophotoraetry method for measuring myoglobin saturation in subcellular volumes: application to resting dog gracilis muscle (Ph.D. Dissertation), University of Rochester: Rochester, N.Y. (1981).

    Google Scholar 

  36. B. M. Fenton, E. K. Rofstad, F. L. Degner, and R. M. Sutherland, Cryospectrophotometric determination of tumour intravascular oxyhemoglobin saturations: dependence on vascular geometry and tumor growth, J. Natl. Cancer Inst. 80:1612 (1988).

    Article  PubMed  CAS  Google Scholar 

  37. C. S. Heacock and R. M. Sutherland, Induction characteristics of oxygen regulated proteins, Int. J. Radiat. Oncol. Biol. Phys. 12:1287–1290 (1986).

    Article  PubMed  CAS  Google Scholar 

  38. C. S. Heacock and R. M. Sutherland, Enhanced synthesis of stress proteins caused by hypoxia and relation to altered cell growth and metabolism, Br. J. Cancer (in press) (1989).

    Google Scholar 

  39. R. E. Wilson, P. C. Keng, and R. M. Sutherland, Drug resistance and Chinese hamster ovary cells during recovery from severe hypoxia, J. Natl. Cancer Inst. 81: 1235–1240) (1989).

    Article  PubMed  CAS  Google Scholar 

  40. T. T. Kwok and R. M. Sutherland, The relationship between radiation response of human squamous carcinoma cells and specific metabolic changes induced by chronic hypoxia, Int. J. Radiat. Oncol. Biol. Phys. 16:1301–1305 (1989).

    Article  PubMed  CAS  Google Scholar 

  41. E. K. Rofstad, R. L. Howell, P. De Muth, T. L. Ceckler, and R. M. Sutherland, 31P NMR spectroscopy in vivo of two murine tumor lines with widely different fractions of radiobiologically hypoxic cells, Int. J. Radiat. Biol. 54:635 (1988).

    Article  PubMed  CAS  Google Scholar 

  42. E. K. Rofstad, P. De Muth, B. M. Fenton, and R. M. Sutherland, 31P Nuclear magnetic resonance spectroscopy studies of tumor energy metabolism and its relationship to intracapillary oxyhemoglobin saturation status and tumor hypoxia, Cancer Res. 48:5440 (1988).

    PubMed  CAS  Google Scholar 

  43. J. J. Sciandra, J. R. Subjeck, and C. S. Hughes, Induction of glucose-regulated proteins during anaerobic exposure and of heat-shock proteins after reoxygenation, PNAS 81:4843 (1984).

    Article  PubMed  CAS  Google Scholar 

  44. R. Sutherland, J. Freyer, W. Mueller-Klieser, R. Wilson, C. Heacock, J. Sciandra, B. Sordat, Cellular growth and metabolic adaptations to nutrient stress and environments in tumor microregions, Int. J. Radiat. Oncol. Biol. Phys. 12:611–615 (1986).

    Article  PubMed  CAS  Google Scholar 

  45. J. Pouyssegur, R. P. C. Shiu, and I. Pastan, Induction of two transformation-sensitive membrane polypeptides in normal fibroblasts by a block in glycoprotein synthesis or glucose deprivation, Cell 11:941 (1977).

    Article  PubMed  CAS  Google Scholar 

  46. W. J. Welch, J. I. Gareels, G. P. Thomas, J. J. Lin, and J. R. Feramisco, Biochemical characterization of the mammalian stress proteins and identification of two stress proteins as glucose and Ca2+-ionophore-regulated proteins, J. Biol. Chem. 258:7102 (1983).

    PubMed  CAS  Google Scholar 

  47. J. J. Sciandra, R. E. Wilson, G. J. Michel, and R. M. Sutherland, in: Proc. of Conf. on Chemical Modifiers of Cancer Treatment, Clearwater, Florida, October (1985).

    Google Scholar 

  48. J. Shen, C. Hughes, C. Chao, J. Cai, C. Bartels, T. Gessner, and J. Subjeck, Coinduction of glucose-regulated proteins and doxuribicin resistance in Chinese hamster cells, Proc. Natl. Acad. Sci. 84:2378 (1987).

    Google Scholar 

  49. A. S. Lee, Coordinated regulation of a set of genes by glucose and calcium ionophores in mammalian cells, Trends Biochem. Sci. 12:20 (1987).

    Article  CAS  Google Scholar 

  50. J. W. Shen, J. R. Subjeck, R. B. Loch, and W. E. Ross, Depletion of topoisomerase II in isolated nuclei during a glucose-regulated stress response, Mol. Cell. Biol. 9:3284 (1989).

    PubMed  CAS  Google Scholar 

  51. W. Mueller-Klieser, S. Walenta, W. Paschen, F. Kallinowski, and P. Vaupel, Metabolic imaging in raicroregions of tumors and normal tissues with bioluminescence and photon counting, J. Natl. Cancer Inst. 80:842 (1988).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. SRI International, 333 Ravenswood Ave., Menlo Park, California, 94025, USA

    Robert M. Sutherland

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  1. Robert M. Sutherland
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Editors and Affiliations

  1. MRC Radiobiology Unit, Didcot, Chilton, Oxon., OX11 ORD, UK

    G. E. Adams  & E. M. Fielden  & 

  2. Facoltà di Farmacia, Istituto di Scienze Chimiche, Università Degli Studi di Bologna, 40127, Bologna, Via S. Donato, 15, Italy

    A. Breccia

  3. CRC Gray Laboratory, Mount Vernon Hospital, Northwood, Middlesex, HA6 2JR, UK

    P. Wardman

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Sutherland, R.M. (1990). Induction of Stress Proteins and Drug Resistance by Hypoxia and Applications of Magnetic Resonance Spectroscopy and Cryospectrophotometry for Detecting Hypoxia in Tumors. In: Adams, G.E., Breccia, A., Fielden, E.M., Wardman, P. (eds) Selective Activation of Drugs by Redox Processes. NATO ASI Series, vol 198. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3768-7_9

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  • DOI: https://doi.org/10.1007/978-1-4615-3768-7_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6679-9

  • Online ISBN: 978-1-4615-3768-7

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