Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1988 Sep;58(3):314–321. doi: 10.1038/bjc.1988.210

pH distributions in spontaneous and isotransplanted rat tumours.

F Kallinowski 1, P Vaupel 1
PMCID: PMC2246588  PMID: 3179183

Abstract

Spontaneous mammary tumours of the rat with various degrees of malignancy exhibit similar tissue pH distributions. The mean pH (+/- s.d.) of dysplasia is 7.05 +/- 0.20. In benign tumours the mean pH is 6.95 +/- 0.19 and in malignant tumours it is 6.94 +/- 0.19. In contrast, tumours with the same degree of malignancy but different histologies show different pH distributions. Benign tumours with a higher percentage of fibrous tissue exhibit less acidic pH values than those with larger portions of epithelial cells (delta pH = 0.38 pH units). The pH distribution in the benign tumours is independent of the tumour wet weight up to stages of very advanced growth. In the malignant tumours, a trend towards more acidic pH values is observed as the tumour mass enlarges. However, in tissue areas within a malignant tumour with gross, long-established necrosis the pH distribution is shifted towards more alkaline pH values. The pH distributions in spontaneous rat tumours are not significantly different from those obtained in isotransplanted Yoshida sarcomas (6.87 +/- 0.21). In the Yoshida sarcomas, mean pH values do not correlate with tumour size. However, a pH gradient from the rim to the centre of the tumours is found which coincides with the development of small, disseminated necroses in the tumour centre. It is concluded that pathology-related variations of tumour pH may be more important than the mode of tumour origin or the degree of malignancy.

Full text

PDF
319

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Acker H., Carlsson J., Stålnacke C. G. Electro-physiological measurements in cultured cellular spheroids. Acta Pathol Microbiol Immunol Scand A. 1983 Mar;91(2):151–160. doi: 10.1111/j.1699-0463.1983.tb02740.x. [DOI] [PubMed] [Google Scholar]
  2. Arnold J. B., Junck L., Rottenberg D. A. In vivo measurement of regional brain and tumor pH using [14C]dimethyloxazolidinedione and quantitative autoradiography. J Cereb Blood Flow Metab. 1985 Sep;5(3):369–375. doi: 10.1038/jcbfm.1985.51. [DOI] [PubMed] [Google Scholar]
  3. Bork R., Vaupel P., Thews G. Atemgas-pH-Nomogramme für das Rattenblut bei 37 degrees C. Anaesthesist. 1975 Feb;24(2):84–90. [PubMed] [Google Scholar]
  4. Borle A. B., Loveday J. Effects of temperature, potassium, and calcium on the electrical potential difference in HeLa cells. Cancer Res. 1968 Dec;28(12):2401–2405. [PubMed] [Google Scholar]
  5. Cole M. A., Crawford D. W., Warner N. E., Puffer H. W. Correlation of regional disease and in vivo PO2 in rat mammary adenocarcinoma. Am J Pathol. 1983 Jul;112(1):61–67. [PMC free article] [PubMed] [Google Scholar]
  6. Dickson J. A., Calderwood S. K. Effects of hyperglycemia and hyperthermia on the pH, glycolysis, and respiration of the Yoshida sarcoma in vivo. J Natl Cancer Inst. 1979 Dec;63(6):1371–1381. [PubMed] [Google Scholar]
  7. Dickson J. A., Ellis H. A. The influence of tumor volume and the degree of heating on the response of the solid Yoshida sarcoma to hyperthermia (40-42 degrees). Cancer Res. 1976 Mar;36(3):1188–1195. [PubMed] [Google Scholar]
  8. Dickson J. A., Suzangar M. In vitro-in vivo studies on the susceptibility of the solid Yoshida sarcoma to drugs and hyperthermia (42 degrees). Cancer Res. 1974 Jun;34(6):1263–1274. [PubMed] [Google Scholar]
  9. EDEN M., HAINES B., KAHLER H. The pH of rat tumors measured in vivo. J Natl Cancer Inst. 1955 Oct;16(2):541–556. [PubMed] [Google Scholar]
  10. Gebert G., Friedman S. M. An implantable glass electrode used for pH measurement in working skeletal muscle. J Appl Physiol. 1973 Jan;34(1):122–124. doi: 10.1152/jappl.1973.34.1.122. [DOI] [PubMed] [Google Scholar]
  11. Gstrein E., Paulmichl M., Lang F. Electrical properties of Ehrlich ascites tumor cells. Pflugers Arch. 1987 May;408(5):432–437. doi: 10.1007/BF00585065. [DOI] [PubMed] [Google Scholar]
  12. Gullino P. M., Grantham F. H., Courtney A. H. Glucose consumption by transplanted tumors in vivo. Cancer Res. 1967 Jun;27(6):1031–1040. [PubMed] [Google Scholar]
  13. Gullino P. M., Grantham F. H., Smith S. H., Haggerty A. C. Modifications of the acid-base status of the internal milieu of tumors. J Natl Cancer Inst. 1965 Jun;34(6):857–869. [PubMed] [Google Scholar]
  14. Hause L. L., Pattillo R. A., Sances A., Jr, Mattingly R. F. Cell surface coatings and membrane potentials of malignant and nonmalignant cells. Science. 1970 Aug 7;169(3945):601–603. doi: 10.1126/science.169.3945.601. [DOI] [PubMed] [Google Scholar]
  15. Hinsull S. M., Colson R. H., Franklin A., Watson B. W., Bellamy D. Determination of extracellular pH and tissue temperature in transplantable rat tumors by use of inductive loop telemetry. J Natl Cancer Inst. 1984 Aug;73(2):463–468. doi: 10.1093/jnci/73.2.463. [DOI] [PubMed] [Google Scholar]
  16. Hochachka P. W., Mommsen T. P. Protons and anaerobiosis. Science. 1983 Mar 25;219(4591):1391–1397. doi: 10.1126/science.6298937. [DOI] [PubMed] [Google Scholar]
  17. Illingworth J. A. A common source of error in pH measurements. Biochem J. 1981 Apr 1;195(1):259–262. doi: 10.1042/bj1950259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jain R. K., Shah S. A., Finney P. L. Continuous noninvasive monitoring of pH and temperature in rat Walker 256 carcinoma during normoglycemia and hyperglycemia. J Natl Cancer Inst. 1984 Aug;73(2):429–436. doi: 10.1093/jnci/73.2.429. [DOI] [PubMed] [Google Scholar]
  19. Jähde E., Rajewsky M. F., Baumgärtl H. pH distributions in transplanted neural tumors and normal tissues of BDIX rats as measured with pH microelectrodes. Cancer Res. 1982 Apr;42(4):1498–1504. [PubMed] [Google Scholar]
  20. Jähde E., Rajewsky M. F. Tumor-selective modification of cellular microenvironment in vivo: effect of glucose infusion on the pH in normal and malignant rat tissues. Cancer Res. 1982 Apr;42(4):1505–1512. [PubMed] [Google Scholar]
  21. KAHLER H., MOORE B. pH of rat tumors and some comparisons with the Lissamine-green circulation test. J Natl Cancer Inst. 1962 Mar;28:561–568. [PubMed] [Google Scholar]
  22. Kallinowski F., Runkel S., Fortmeyer H. P., Förster H., Vaupel P. L-glutamine: a major substrate for tumor cells in vivo? J Cancer Res Clin Oncol. 1987;113(3):209–215. doi: 10.1007/BF00396375. [DOI] [PubMed] [Google Scholar]
  23. Kallinowski F., Vaupel P. Concurrent measurements of O2 partial pressures and pH values in human mammary carcinoma xenotransplants. Adv Exp Med Biol. 1986;200:609–621. doi: 10.1007/978-1-4684-5188-7_74. [DOI] [PubMed] [Google Scholar]
  24. Koeze T. H., Lantos P. L., Iles R. A., Gordon R. E. In vivo nuclear magnetic resonance spectroscopy of a transplanted brain tumour. Br J Cancer. 1984 Mar;49(3):357–361. doi: 10.1038/bjc.1984.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Komitowski D., Sass B., Laub W. Rat mammary tumor classification: notes on comparative aspects. J Natl Cancer Inst. 1982 Jan;68(1):147–156. [PubMed] [Google Scholar]
  26. MEYER K. A., KAMMERLING E. M. pH studies of malignant tissues in human beings. Cancer Res. 1948 Nov;8(11):513–518. [PubMed] [Google Scholar]
  27. Müller-Klieser W., Vaupel P., Manz R., Grunewald W. A. Intracapillary oxyhemoglobin saturation in malignant tumours with central or peripheral blood supply. Eur J Cancer. 1980 Feb;16(2):195–201. doi: 10.1016/0014-2964(80)90151-6. [DOI] [PubMed] [Google Scholar]
  28. Osinsky S., Bubnovskaja L., Sergienko T. Tumour pH under induced hyperglycemia and efficacy of chemotherapy. Anticancer Res. 1987 Mar-Apr;7(2):199–201. [PubMed] [Google Scholar]
  29. Redmann K. Elektrophysiologischer in vitro-Nachweis einer individuellen Ouabain-Empfindlichkeit menschlicher Ovarialtumoren. Acta Biol Med Ger. 1981;40(2):153–160. [PubMed] [Google Scholar]
  30. Rhee J. G., Kim T. H., Levitt S. H., Song C. W. Changes in acidity of mouse tumor by hyperthermia. Int J Radiat Oncol Biol Phys. 1984 Mar;10(3):393–399. doi: 10.1016/0360-3016(84)90060-9. [DOI] [PubMed] [Google Scholar]
  31. Révész L., Siracka E. Tumor vascularization, hypoxia, staging of tumors and radiocurability. Strahlentherapie. 1984 Nov;160(11):658–660. [PubMed] [Google Scholar]
  32. SCHEID P., KUNZE P. Continuous vital pH-measurement in animal tumours under (additional) metabolic stress. Acta Unio Int Contra Cancrum. 1962;18:256–258. [PubMed] [Google Scholar]
  33. Schauble M. K., Habal M. B. Electropotentials of surgical specimens. Arch Pathol. 1970 Nov;90(5):411–415. [PubMed] [Google Scholar]
  34. Song C. W., Kang M. S., Rhee J. G., Levitt S. H. The effect of hyperthermia on vascular function, pH, and cell survival. Radiology. 1980 Dec;137(3):795–803. doi: 10.1148/radiology.137.3.7444064. [DOI] [PubMed] [Google Scholar]
  35. TAGASHIRA Y., TAKEDA S., KAWANO K., AMANO S. Continuous pH measuring by means of microglass electrode inserted in living normal and tumor tissues (2nd report), with an additional report on interaction of SH-group of animal protein with carcinogenic agent in the carcinogenetic mechanism. Gan. 1954 Sep;45(2-3):99–101. [PubMed] [Google Scholar]
  36. TAGASHIRA Y., YASUHIRA K., MATSUO H., AMANO S. [Continual pH measuring by means of inserted microglass electrode in living normal and tumor tissues. I]. Gan. 1953 Sep;44(2-3):63–64. [PubMed] [Google Scholar]
  37. Thistlethwaite A. J., Leeper D. B., Moylan D. J., 3rd, Nerlinger R. E. pH distribution in human tumors. Int J Radiat Oncol Biol Phys. 1985 Sep;11(9):1647–1652. doi: 10.1016/0360-3016(85)90217-2. [DOI] [PubMed] [Google Scholar]
  38. Timmermann J., von Buttlar M. Membranpotentialuntersuchungen an menschlichen Epithelkarzinomzellen unter ionisierender Bestrahlung. Strahlentherapie. 1978 Oct;154(10):700–702. [PubMed] [Google Scholar]
  39. Vaupel P. W., Frinak S., Bicher H. I. Heterogeneous oxygen partial pressure and pH distribution in C3H mouse mammary adenocarcinoma. Cancer Res. 1981 May;41(5):2008–2013. [PubMed] [Google Scholar]
  40. Vaupel P., Gabbert H. Evidence for and against a tumor type-specific vascularity. Strahlenther Onkol. 1986 Oct;162(10):633–638. [PubMed] [Google Scholar]
  41. Walliser S., Redmann K. Effect of 5-fluorouracil and thymidine on the transmembrane potential and zeta potential of HeLa cells. Cancer Res. 1978 Oct;38(10):3555–3559. [PubMed] [Google Scholar]
  42. Wike-Hooley J. L., Haveman J., Reinhold H. S. The relevance of tumour pH to the treatment of malignant disease. Radiother Oncol. 1984 Dec;2(4):343–366. doi: 10.1016/s0167-8140(84)80077-8. [DOI] [PubMed] [Google Scholar]
  43. Wike-Hooley J. L., van den Berg A. P., van der Zee J., Reinhold H. S. Human tumour pH and its variation. Eur J Cancer Clin Oncol. 1985 Jul;21(7):785–791. doi: 10.1016/0277-5379(85)90216-0. [DOI] [PubMed] [Google Scholar]
  44. van den Berg A. P., Wike-Hooley J. L., van den Berg-Blok A. E., van der Zee J., Reinhold H. S. Tumour pH in human mammary carcinoma. Eur J Cancer Clin Oncol. 1982 May;18(5):457–462. doi: 10.1016/0277-5379(82)90114-6. [DOI] [PubMed] [Google Scholar]
  45. von Ardenne M., Reitnauer P. G. Verstärkung der mit Glukoseinfusion erzielbaren Tumorübersäuerung durch lokale Hyperthermie. Res Exp Med (Berl) 1979 Apr 23;175(1):7–18. doi: 10.1007/BF01851229. [DOI] [PubMed] [Google Scholar]
  46. von Ardenne M., Reitnauer P. G. Verstärkung der mit Glukoseinfusion erzielbaren Tumorübersäuerung in vivo durch NAD. Arch Geschwulstforsch. 1976;46(3):197–203. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES