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British Journal of Cancer logoLink to British Journal of Cancer
. 1982 Feb;45(2):256–264. doi: 10.1038/bjc.1982.41

Oxygen tensions in multicell spheroids of two cell lines.

W F Mueller-Klieser, R M Sutherland
PMCID: PMC2010909  PMID: 7059474

Abstract

O2 tensions (Po2) were measured with microelectrodes in multicellular spheroids from EMT6/Ro and V-79-171-B cells. The measurements were performed in spheroids kept in flowing growth medium that was equilibrated with 5% CO2 and air at a temperature of 37 degrees C and contained 5.5 mM glucose. The recorded Po2 profiles are characterized by a diffusion-depleted zone surrounding the spheroids and by a steep drop in Po2 within the spheroids over mean distance of 220 and 188 micrometer from the surface of EMT6/Ro and V-79-171B spheroids over mean distance of 220 and 188 micrometer from the surface of EMT6/Ro and V-79-171B spheroids respectively. Smaller spheroid exhibit parabolic Po2 profiles, larger ones show a central plateau. The region of the steep decrease in Po2 corresponds to the thickness of the viable rim: the plateau region is created by the absence of O2 consumption in the central necrotic area. Po2 in the centre of EMT6/Ro spheroids decreased from 66 mmHg at a diameter of 400 micrometer to 13 mmHg at a diameter of 1000 micrometer. Under the present conditions during growth and in the experiments, values below 5 mmHg were recorded only in spheroids 1200 micrometer. Comparably low Po2 was recorded in V-79 spheroids with diameters of 650 micrometer +. In spheroids of this cell type with a diameter of 400 micrometer, Po2 was 42 mmHg. The findings provide evidence that necrosis may arise at average Po2 of 57 and 42 mmHg in EMT6/Ro and V-79-171B spheroids, respectively, grown under the conditions described.

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Selected References

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  1. Bock P. E., Frieden C. Phosphofructokinase. I. Mechanism of the pH-dependent inactivation and reactivation of the rabbit muscle enzyme. J Biol Chem. 1976 Sep 25;251(18):5630–5636. [PubMed] [Google Scholar]
  2. Carlsson J., Stålnacke C. G., Acker H., Haji-Karim M., Nilsson S., Larsson B. The influence of oxygen on viability and proliferation in cellular spheroids. Int J Radiat Oncol Biol Phys. 1979 Nov-Dec;5(11-12):2011–2020. doi: 10.1016/0360-3016(79)90953-2. [DOI] [PubMed] [Google Scholar]
  3. Crabtree H. G. Observations on the carbohydrate metabolism of tumours. Biochem J. 1929;23(3):536–545. doi: 10.1042/bj0230536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. FROESE G. The respiration of ascites tumour cells at low oxygen concentrations. Biochim Biophys Acta. 1962 Mar 12;57:509–519. doi: 10.1016/0006-3002(62)91158-7. [DOI] [PubMed] [Google Scholar]
  5. Franko A. J., Sutherland R. M. Oxygen diffusion distance and development of necrosis in multicell spheroids. Radiat Res. 1979 Sep;79(3):439–453. [PubMed] [Google Scholar]
  6. Franko A. J., Sutherland R. M. Radiation survival of cells from spheroids grown in different oxygen concentrations. Radiat Res. 1979 Sep;79(3):454–467. [PubMed] [Google Scholar]
  7. Franko A. J., Sutherland R. M. Rate of death of hypoxic cells in multicell spheroids. Radiat Res. 1978 Dec;76(3):561–572. [PubMed] [Google Scholar]
  8. Freyer J. P., Sutherland R. M. Selective dissociation and characterization of cells from different regions of multicell tumor spheroids. Cancer Res. 1980 Nov;40(11):3956–3965. [PubMed] [Google Scholar]
  9. Gosalvez M., Weinhouse S. Control mechanisms of oxygen and glucose utilization in tumours. Adv Exp Med Biol. 1976;75:587–596. doi: 10.1007/978-1-4684-3273-2_69. [DOI] [PubMed] [Google Scholar]
  10. Kaufman N., Bicher H. I., Hetzel F. W., Brown M. A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids. Cancer Clin Trials. 1981;4(2):199–204. [PubMed] [Google Scholar]
  11. Koch C. J., Biaglow J. E. Respiration of mammalian cells at low concentrations of oxygen: I. Effect of hypoxic-cell radiosensitizing drugs. Br J Cancer Suppl. 1978 Jun;3:163–167. [PMC free article] [PubMed] [Google Scholar]
  12. Mueller-Klieser W., Vaupel P., Manz R., Schmidseder R. Intracapillary oxyhemoglobin saturation of malignant tumors in humans. Int J Radiat Oncol Biol Phys. 1981 Oct;7(10):1397–1404. doi: 10.1016/0360-3016(81)90036-5. [DOI] [PubMed] [Google Scholar]
  13. Schneiderman G., Goldstick T. K. Oxygen electrode design criteria and performance characteristics: recessed cathode. J Appl Physiol Respir Environ Exerc Physiol. 1978 Jul;45(1):145–154. doi: 10.1152/jappl.1978.45.1.145. [DOI] [PubMed] [Google Scholar]
  14. Sutherland R. M., Durand R. E. Hypoxic cells in an in vitro tumour model. Int J Radiat Biol Relat Stud Phys Chem Med. 1973 Mar;23(3):235–246. doi: 10.1080/09553007314550261. [DOI] [PubMed] [Google Scholar]
  15. Sutherland R. M., Durand R. E. Radiation response of multicell spheroids--an in vitro tumour model. Curr Top Radiat Res Q. 1976 Jan;11(1):87–139. [PubMed] [Google Scholar]
  16. Sutherland R. M., McCredie J. A., Inch W. R. Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. J Natl Cancer Inst. 1971 Jan;46(1):113–120. [PubMed] [Google Scholar]
  17. Tannock I. F. Oxygen diffusion and the distribution of cellular radiosensitivity in tumours. Br J Radiol. 1972 Jul;45(535):515–524. doi: 10.1259/0007-1285-45-535-515. [DOI] [PubMed] [Google Scholar]
  18. Vaupel P. Hypoxia in neoplastic tissue. Microvasc Res. 1977 May;13(3):399–408. doi: 10.1016/0026-2862(77)90106-6. [DOI] [PubMed] [Google Scholar]
  19. Vaupel P., Manz R., Müller-Klieser W., Grunewald W. A. Intracapillary HbO2 saturation in malignant tumors during normoxia and hyperoxia. Microvasc Res. 1979 Mar;17(2):181–191. doi: 10.1016/0026-2862(79)90405-9. [DOI] [PubMed] [Google Scholar]
  20. Vaupel P., Thews G. Pathophysiological aspects of glucose uptake by the tumor tissue under various conditions of oxygen and glucose supply. Adv Exp Med Biol. 1976;75:547–553. doi: 10.1007/978-1-4684-3273-2_64. [DOI] [PubMed] [Google Scholar]
  21. Whalen W. J., Nair P., Ganfield R. A. Measurements of oxygen tension in tissues with a micro oxygen electrode. Microvasc Res. 1973 May;5(3):254–262. doi: 10.1016/0026-2862(73)90035-6. [DOI] [PubMed] [Google Scholar]
  22. Whalen W. J., Nair P. Intracellular PO2 and its regulation in resting skeletal muscle of the guinea pig. Circ Res. 1967 Sep;21(3):251–261. doi: 10.1161/01.res.21.3.251. [DOI] [PubMed] [Google Scholar]
  23. Whalen W. J., Savoca J., Nair P. Oxygen tension measurements in carotid body of the cat. Am J Physiol. 1973 Oct;225(4):986–991. doi: 10.1152/ajplegacy.1973.225.4.986. [DOI] [PubMed] [Google Scholar]
  24. ZWARTOUW H. T., WESTWOOD J. C. Factors affecting growth and glycolysis in tissue culture. Br J Exp Pathol. 1958 Oct;39(5):529–539. [PMC free article] [PubMed] [Google Scholar]

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