Blood Flow, Tissue Oxygenation, pH Distribution, and Energy Metabolism of Murine Mammary Adenocarcinomas During Growth

  • P. Vaupel
  • P. Okunieff
  • L. J. Neuringer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 248)


Many solid tumors are relatively resistant to non-surgical therapeutic assaults. A variety of factors are involved in the lack of responsiveness of these neoplasms including cellular heterogeneity due to genetic differences between cells, and physiological factors created by inadequate and heterogeneous vascular networks. Thus, properties such as tumor blood flow, tissue oxygenation, pH distribution and energy metabolism, factors which generally go hand in hand, markedly influence the therapeutic response. Since the strategic approach must consider the physiological microenviron-ment of the cells within a tumor mass and -if possible- should exploit the metabolic micromilieu in designing therapies, we have measured relevant parameters in a well established murine tumor cell line with a known size dependent increase in the radiobiologicaly hypoxic cell fraction.


Tumor Volume Mammary Tumor Tissue Oxygenation Tumor Blood Flow Murine Mammary Tumor 
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  1. 1.
    Sedlacek, R.S., and Mason, K.S., 1977, A simple and inexpensive method for maintaining a defined flora mouse colony, Lab. Anim. Sci., 27:667.PubMedGoogle Scholar
  2. 2.
    Stosseck, K., Luebbers, D.W., and Cottin, N., 1974, Determination of local blood flow (microflow) by electrochemically generated hydrogen. Construction and application of the measuring probe, Pfluegers Arch., 348: 225.CrossRefGoogle Scholar
  3. 3.
    Bicher, H.I., Hetzel, F.W., Sandhu, T.S., Frinak, S., Vaupel, P., O’Hara, M.D., and O’Brien, T., 1980, Effects of hyperthermia on normal and tumor microenvironment, Radiology, 137: 523.PubMedGoogle Scholar
  4. 4.
    Vaupel, P.W., Frinak, S., and Bicher, H.I., 1981, Heterogeneous oxygen partial pressure and pH distribution in C3H mouse mammary adenocarcinoma, Cancer Res., 41: 2008.PubMedGoogle Scholar
  5. 5.
    Okunieff, P., Ramsay, J., Tokuhiro, T., Hitzig, B.M., Rummeny, E., Neu-ringer, L.J., and Suit, H.D., 1988, Estimation of tumor oxygen and metabolic rate using P MRS: Correlation of longitudinal relaxation with tumor growth rate and DNA synthesis, Int. J. Radiat. Oncol. Biol. Phys., 14: 1185.PubMedCrossRefGoogle Scholar
  6. 6.
    Okunieff, P., Rummeny, E., Vaupel, P., Skates, S., Willett, C., Hitzig, B.M., Neuringer, L.J., and Suit H.D., 1988, Effects of pentobarbital anesthesia on the energy metabolism of murine tumors studied by in vivo 31P nuclear magnetic resonance spectroscopy, Radiat. Res., in press.Google Scholar
  7. 7.
    Moon. R.B., and Richards, J.H., 1973, Determination of intracellular pH by 31P NMR, J. Biol. Chem., 248: 7276.PubMedGoogle Scholar
  8. 8.
    Vaupel, P., Fortmeyer, H.P., Runkel, S., and Kallinowski, F., 1987, Blood flow, oxygen consumption, and tissue oxygenation of human breast cancer xenografts in nude rats, Cancer Res., 47: 3496.PubMedGoogle Scholar
  9. 9.
    Tozer, G., Suit, H.D., Barlai-Kovach, M., Brunengraber, H., and Biaglow, J., 1987, Energy metabolism and blood perfusion in a mouse mammary adenocarcinoma during growth and following X irradiation, Radiat. Res., 109: 275.PubMedCrossRefGoogle Scholar
  10. 10.
    Kallinowski, F., and Vaupel, P., 1988, pH distributions in spontaneous and isotransplanted rat tumors, Brit. J. Cancer, in press.Google Scholar
  11. 11.
    Steen, R.G., Tamargo, R.J., McGovern, K.A., Rajan. S.S., Brem, H., Wehrle, J.P., and Glickson, J.D., 1988, In vivo 31P nuclear magnetic resonance spectroscopy of subcutaneous 9L gliosarcoma: Effects of tumor growth and treatment with l,3-Bis(2-chloroethyl)-l-nitrosourea on tumor bioenergetics and histology, Cancer Res., 48: 676.PubMedGoogle Scholar
  12. 12.
    Okunieff, P.G., Koutcher, J.A., Gerweck, L., McFarland, E., Hitzig, B., Urano, M., Brady, T., Neuringer, L.J., and Suit, H.D., 1986. Tumor size dependent changes in a murine fibrosarcoma: Use of in vivo P NMR for non-invasive evaluation of tumor metabolic status, Int. J. Radiat. Oncol. Biol. Phys., 12: 793.PubMedCrossRefGoogle Scholar
  13. 13.
    Okunieff, P., Kallinow,ski, F., Vaupel, P., and Neuringer, L.J., 1988, Effects of hydralazine-induced vasodilation on the energy metabolism of murine tumors studied by in vivo P nuclear magnetic resonance spectroscopy, J. Natl. Cancer Inst., 80: 745.PubMedCrossRefGoogle Scholar
  14. 14.
    Kallinowski, F., Tyler, G., Mueller-Klieser, W., and Vaupel, P., 1989, Growth related changes of oxygen consumption rates of tumor cells grown in vitro and in vivo, J. Cell. Physiol., submitted.Google Scholar
  15. 15.
    Evelhoch, J.L., Sapareto, S.A., Jick, D.E.L., and Ackerman, J.J.H.,1984, In vivo metabolic effects of hyperglycemia in murine radiation-induced fibrosarcoma: A 31P NMR investigation, Proc. Natl. Acad. Sci. USA, 81: 6496.PubMedCrossRefGoogle Scholar
  16. 16.
    Vaupel, P., and Hammersen, F. (eds.), 1983, “Mikrozirkulation in malignen Tumoren”, Karger, Basel, Muenchen, Paris, London, New York, Tokyo, Sydney.Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • P. Vaupel
    • 1
  • P. Okunieff
    • 1
  • L. J. Neuringer
    • 2
  1. 1.Dept. Radiation MedicineMassachusetts General Hospital Cancer Center, Harvard Medical SchoolBostonUSA
  2. 2.Francis Bitter National Magnet LaboratoryMassachusetts Institute of TechnologyCambridgeUSA

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