Summary
Using the method described by Gullino and Grantham (1961), we implanted cells of DS-carcinosarcoma into rat kidneys where they were maintained as “tissue-isolated”. After an average of 11 days the infiltrating and destructively growing tumor replaced the kidney tissue almost completely. The tumor-kidney mass was connected with the host by only a single artery and vein.
The determination of tumor blood-flow was made, keeping the pressure constant, after canulating the tumor vein with the help of a burette by means of a roller pump and an air-regulator. At the same time micro blood samples from the tumor vein and the aorta were taken under anaerobic conditions to determine pH, \({\text{p}}_{O_{\text{2}} } \), \({\text{p}}_{CO_{\text{2}} } \), Hb-concentration and hematocrit. By calculating the arterio-venous difference in oxygen content and the tumor blood-flow we were able to determine oxygen consumption of the implanted tumors in vivo. The average blood-flow of 27 measurements in 16 tumors was \(\dot Q\)=6.4 ml/100 g/min and the utilization of oxygen was \(\dot V_{0_2 } \) = 0.5 mlO2/100 g/min. An explanation for the relatively high venous \({\text{P}}_{{\text{O}}_{\text{2}} } \) is offered by a dextroposition of the oxygen dissociation curve, by pH-lowering, by \({\text{p}}_{CO_{\text{2}} } \)-increase and anemia as well as especially by the small oxygen utilization of the tumor cells themselves. Under in vivo conditions the small blood-flow of the tumor may be the limiting factor in the oxygen supply of the tumor.
Zusammenfassung
Nach einer von Gullino u. Grantham (1961) angegebenen Methode wurden DS-Carcino-Sarkomzellen in Rattennieren verimpft und gewebsisoliert gezüchtet. Nach im Mittel 11 Tagen hat der infiltrierend und destruierend wachsende Tumor das Nierengewebe meist völlig ersetzt und steht mit dem Wirtstier nur über eine Arterie und eine Vene in Verbindung. Die Tumordurchblutungsmessungen erfolgten nach Kanulierung der Tumorvene druckkonstant mit Hilfe eines Rollenpumpen-Windkessel-Systems über eine Meßcapillare. Gleichzeitig konnten Mikroblutproben unter Luftabschluß aus Tumorvene und Aorta entnommen und pH, O2-Druck, CO2-Druck, Hb-Konzentration und Hämatokrit bestimmt werden. Aus der errechneten arterio-venösen O2-Differenz und der Tumordurchblutung ließ sich der Sauerstoffverbrauch der Impftumoren in vivo bestimmen. Als Mittelwerte von 27 Messungen an 16 Tumoren ergab sich für die Durchblutung\(\dot Q\)=6,4 ml Blut/100 g/min und für den Sauerstoffverbrauch \(\dot V_{0_2 } \) = 0.5 mlO2/100 g/min. Als ursächlich für den relativ hohen mittleren Sauerstoffpartialdruck im venösen Blut werden eine Rechtsverlagerung der Sauerstoffbindungskurve durch pH-Erniedrigung, CO2-Druckerhöhung und Anämie sowie vor allem der geringe Sauerstoffverbrauch der Tumorzellen angesehen. Unter in vivo-Bedingungen ist die geringe Tumordurchblutung als möglicherweise limitierender Faktor der Sauerstoffversorgung des Tumors anzunehmen.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Literatur
Asmussen, E., Christensen, E. H., Nielsen, M.: Die O2-Aufnahme der ruhenden und der arbeitenden Skeletmuskeln. Scand. Arch. Physiol. 82, 212 (1939).
Atkins, H. L., Seaman, W. B., Jacox, H. W., Matteo, R. S.: Experience with hyperbaric oxygenation in clinical radiotherapy. Amer. J. Roentgenol. 93, 651 (1965).
Bierman, H. R., Kelly, K. H., Singer, G.: Studies of the blood supply of tumours in man. IV. The increased oxygen content of venous blood draining neoplasm. J. nat. Cancer. Inst. 12, 701 (1952).
Bing, R. J.: The coronary circulating in health and disease as studied by coronary sinus catheterization. Bull. Acad. Med. 27, 407 (1951).
Cataland, S., Cohen, C., Sapirstein, L. A.: Relationship between size and perfusion rate of transplanted tumors. J. nat. Cancer Inst. 29, 389 (1962).
Cater, D. B.: Oxygen tension in neoplastic tissues. Tumori 50, 435 (1964).
—, Silver, I. A.: Quantitative measurements of oxygen tension in normal tissues and in the tumours of patients before and after radiotherapy. Acta Radiol. 53, 233 (1960).
——, Wilson, G. M.: Apparatus and technique for the quantitative measurement of oxygen tension in living tissues. Proc. roy. Soc. B. 151, 256 (1960).
Cater, D. B.: Schoeninger, E. L., Watkinson, D. A.: Effect on oxygen tension of tumours of breathing oxygen at high pressures. Lancet 1962II, 381.
Churchill-Davidson, I.: High-pressure oxygen and radiotherapy. Anglo. German. Med. Rev. 2, 519 (1964).
Evans, N. T. S.: The effect of oxygen breathing and radiotherapy upon the tissue oxygen tension of some human tumours. Brit. J. Radiol. 36, 418 (1963).
—, Naylor, P. F. D.: The measurement of partial pressure of oxygen in vivo. J. Polarogr. Soc. 2, 26 (1960).
Gahlenbeck, H.: Persönliche Mitteilung. Physiol. Institut der Med. Hochschule Hannover.
Gray, L. H., Conger, A. D., Ebert, M., Hornsey, S., Scott, O. C. A.: The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Brit. J. Radiol. 26, 638 (1953).
Greenstein, J. Ph.: Biochemistry of Cancer. New York: Academic Press 1954.
Grote, J., Kreuscher, H.: Die Sauerstoffversorgung des Hundegehirns. I. Mitteilung: Die cerebrale Durchblutung und Sauerstoffaufnahme. Zool. Anz. 179, 319 (1967).
Gullino, P. M., Grantham, F. H.: Studies on the exchange of fluids between host and tumor. I. A method for growing “tissue-isolated” tumors in laboratory animals. J. nat. Cancer Inst. 27, 679 (1961).
——: Studies on the exchange of fluids between host and tumor. II. The blood flow of hepatomas and other tumors in rats and mice. J. nat. Cancer Inst. 27, 1465 (1961).
——: Studies on the exchange of fluids between host and tumor. III. Regulation of blood flow in hepatomas and other rat tumors. J. nat. Cancer Inst. 28, 211 (1962).
——, Courtey, A. H.: Utilization of oxygen by transplanted tumors in vivo. Cancer Res. 27, 1020 (1967).
——, Smith, S. H., Haggerty, A. C.: Modifications of the acid-base status of the internal milieu of tumors. J. nat. Cancer Inst. 34, 857 (1965).
Gump, F. E., White, R. L.: Determination of regional tumor blood flow by Krypton-85. Cancer 21, 871 (1968).
Howard-Flanders, P., Scott, O. C. A.: Tissue oxygen tension and radiotherapy. Radiology 74, 956 (1960).
Hultborn, K. A., Forssberg, A. G.: Irradiation of skin tumors during pure oxygen inhalation. Acta Radiol. 42, 475 (1954).
Jamieson, D., van den Brenk, H. A. S.: Comparison of oxygen tensions in normal tissues and Yoshida sarcoma of the rat breathing air or oxygen at 4 atmospheres. Brit. J. Cancer 17, 70 (1963).
——: Oxygen tension in human malignant disease under hyperbaric conditions. Brit. J. Cancer 19, 139 (1965).
Kramer, K., Deetjen, P.: Beziehungen des O2-Verbrauchs der Niere zu Durchblutung und Glomerulusfiltrat bei Änderung des arteriellen Druckes. Pflügers Arch. ges. Physiol. 271, 782 (1960).
Kruuv, J., Inch, W. R., McCredie, J. A.: Effects of breathing gases containing oxygen and carbon dioxide at 1 and 3 atmospheres pressures on blood flow and oxygenation of tumors. Can. J. Physiol. Pharmacol. 45, 49 (1967).
Meyers, J. D., Hickam, J. B.: An estimation of the hepatic flow and splanchnic oxygen consumption in heart failure. J. clin. Invest. 27, 620 (1948).
Ross, R. S., Ueda, K., Lichtlen, P. R., Rees, J. R.: Measurement of myocardial blood flow in animals and man by selective injection of radioactive inert gas into the coronary arteries. Circulation Res. 15, 28 (1964).
Rubin, P., Casarett, G.: Microcirculation of tumors. Part 1: Anatomy, function, and necrosis. Clin. Radiol. 17, 220 (1966).
Schulz, J., Müller, H.: Haemogramm of normal and starved rats. Nature (Lond.) 196, 178 (1962).
Seaman, W. B., Tapley, N. V., Sanger, C., Jacox, H. W., Atkins, H. L.: Combined high-pressure oxygen and radiation therapy in treatment of human cancer. Amer. j. Roentgenol. 85, 816 (1961).
Selkurt, E. E.: Validity of the bromsulphthalein (BSP) method for estimating hepatic blood flow. Amer. J. Physiol. 175, 461 (1953).
Severinghaus, J. W.: Blood gas calculator. J. appl. Physiol. 21, 1108 (1966).
Siegenthaler, W.: Klinische Pathophysiologie. Stuttgart: Georg Thieme 1970.
Urbach, F.: Pathophysiology of malignacy: I. Tissue oxygen tension of benign and malignant tumors of the skin. Proc. Soc. exp. Biol. 92, 644 (1956).
Waldeck, F.: Ein heizbarer Operationstisch mit Regelvorrichtung zur Konstanthaltung der Körpertemperatur narkotisierter Kleintiere. Pflügers Arch. ges. Physiol. 310, 189 (1969).
Warburg, O., Minami, S.: Versuche an überlebendem Carcinomgewebe. Klin. Wschr. 17, 776 (1923).
Wildermuth, O.: Hyperbaric radiotherapy: some observations in the development of clinical application and technique. Amer. J. Roentgenol. 96, 171 (1966).
Wollman, S. H., Reed, F. E.: Clearance of blood radioiodide by transplantable tumors of the thyroid gland in the unanaestetized rat. J. nat. Cancer Inst. 31, 1479 (1963).
Author information
Authors and Affiliations
Additional information
Mit Unterstützung durch die Landesversicherungsanstalt Rheinland-Pfalz Speyer/Rh.
Rights and permissions
About this article
Cite this article
Schwarz, W., Schulz, V., Kersten, M. et al. Durchblutung und Sauerstoffverbrauch gewebsisolierter Impftumoren (DS-Carcinosarkom) in vivo. Z Krebs-forsch 75, 161–173 (1971). https://doi.org/10.1007/BF00524512
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00524512