Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1991 Nov;64(5):862–866. doi: 10.1038/bjc.1991.414

In vivo 31P nuclear magnetic resonance spectroscopy of experimental murine tumours and human tumour xenografts: effects of blood flow modification.

J C Bremner 1, C J Counsell 1, G E Adams 1, I J Stratford 1, P J Wood 1, J F Dunn 1, G K Radda 1
PMCID: PMC1977471  PMID: 1931606

Abstract

The effect of hydralazine on tumours appears to vary depending on tumour type. Blood flow and radiation sensitivity decrease more in murine tumours than human tumour xenografts. In this study a comparison between various tumour types has been made using in vivo 31P nuclear magnetic resonance spectroscopy (NMRS) to follow the metabolic responses occurring after clamping or intravenous administration of hydralazine (5 mg kg-1). Large increases in the Pi/total phosphate ratio were found with the murine sarcomas, KHT and RIF-1 implanted into C3H/He mice. However little or no effect was seen for the two human xenografted tumours, HX118 and HT29 implanted in MFI nu/nu/01a mice. An intermediate response was observed for KHT tumours grown in nu/nu mice. All tumours showed a large response to clamping. The anaesthetic Hypnorm/Hypnovel has a great influence on the response of the tumour metabolism to hydralazine appearing to both prolong and increase the changes induced. There is evidence to support the theory that the changes in 31P spectra are related to the oxygen status of the tumours.

Full text

PDF
862

Selected References

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

  1. Bhujwalla Z. M., Tozer G. M., Field S. B., Maxwell R. J., Griffiths J. R. The energy metabolism of RIF-1 tumours following hydralazine. Radiother Oncol. 1990 Nov;19(3):281–291. doi: 10.1016/0167-8140(90)90155-p. [DOI] [PubMed] [Google Scholar]
  2. Brown T. R., Graham R. A., Szwergold B. S., Thoma W. J., Meyer R. A. Phosphorylated metabolites in tumors, tissues, and cell lines. Ann N Y Acad Sci. 1987;508:229–240. doi: 10.1111/j.1749-6632.1987.tb32907.x. [DOI] [PubMed] [Google Scholar]
  3. Chaplin D. J., Acker B. The effect of hydralazine on the tumor cytotoxicity of the hypoxic cell cytotoxin RSU-1069: evidence for therapeutic gain. Int J Radiat Oncol Biol Phys. 1987 Apr;13(4):579–585. doi: 10.1016/0360-3016(87)90075-7. [DOI] [PubMed] [Google Scholar]
  4. Chaplin D. J. Postirradiation modification of tumor blood flow: a method to increase the effectiveness of chemical radiosensitizers. Radiat Res. 1988 Aug;115(2):292–302. [PubMed] [Google Scholar]
  5. Cole S., Stratford I. J., Adams G. E. Manipulation of radiobiological hypoxia in a human melanoma xenograft to exploit the bioreductive cytotoxicity of RSU-1069. Int J Radiat Biol. 1989 Nov;56(5):587–591. doi: 10.1080/09553008914551781. [DOI] [PubMed] [Google Scholar]
  6. Denekamp J., Hill S. A., Hobson B. Vascular occlusion and tumour cell death. Eur J Cancer Clin Oncol. 1983 Feb;19(2):271–275. doi: 10.1016/0277-5379(83)90426-1. [DOI] [PubMed] [Google Scholar]
  7. Dunn J. F., Frostick S., Adams G. E., Stratford I. J., Howells N., Hogan G., Radda G. K. Induction of tumour hypoxia by a vasoactive agent. A combined NMR and radiobiological study. FEBS Lett. 1989 Jun 5;249(2):343–347. doi: 10.1016/0014-5793(89)80655-6. [DOI] [PubMed] [Google Scholar]
  8. Evelhoch J. L., Sapareto S. A., Nussbaum G. H., Ackerman J. J. Correlations between 31P NMR spectroscopy and 15O perfusion measurements in the RIF-1 murine tumor in vivo. Radiat Res. 1986 Apr;106(1):122–131. [PubMed] [Google Scholar]
  9. Horsman M. R., Brown J. M., Hirst V. K., Lemmon M. J., Wood P. J., Dunphy E. P., Overgaard J. Mechanism of action of the selective tumor radiosensitizer nicotinamide. Int J Radiat Oncol Biol Phys. 1988 Sep;15(3):685–690. doi: 10.1016/0360-3016(88)90312-4. [DOI] [PubMed] [Google Scholar]
  10. Jirtle R. L. Chemical modification of tumour blood flow. Int J Hyperthermia. 1988 Jul-Aug;4(4):355–371. doi: 10.3109/02656738809016490. [DOI] [PubMed] [Google Scholar]
  11. Kalmus J., Okunieff P., Vaupel P. Dose-dependent effects of hydralazine on microcirculatory function and hyperthermic response of murine FSall tumors. Cancer Res. 1990 Jan 1;50(1):15–19. [PubMed] [Google Scholar]
  12. Mueller-Klieser W., Schaefer C., Walenta S., Rofstad E. K., Fenton B. M., Sutherland R. M. Assessment of tumor energy and oxygenation status by bioluminescence, nuclear magnetic resonance spectroscopy, and cryospectrophotometry. Cancer Res. 1990 Mar 15;50(6):1681–1685. [PubMed] [Google Scholar]
  13. Okunieff P., Kallinowski F., Vaupel P., Neuringer L. J. Effects of hydralazine-induced vasodilation on the energy metabolism of murine tumors studied by in vivo 31P-nuclear magnetic resonance spectroscopy. J Natl Cancer Inst. 1988 Jul 20;80(10):745–750. doi: 10.1093/jnci/80.10.745. [DOI] [PubMed] [Google Scholar]
  14. Rowell N. P., Flower M. A., McCready V. R., Cronin B., Horwich A. The effects of single dose oral hydralazine on blood flow through human lung tumours. Radiother Oncol. 1990 Aug;18(4):283–292. doi: 10.1016/0167-8140(90)90108-9. [DOI] [PubMed] [Google Scholar]
  15. Stratford I. J., Adams G. E., Godden J., Nolan J., Howells N., Timpson N. Potentiation of the anti-tumour effect of melphalan by the vasoactive agent, hydralazine. Br J Cancer. 1988 Aug;58(2):122–127. doi: 10.1038/bjc.1988.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Twentyman P. R., Brown J. M., Gray J. W., Franko A. J., Scoles M. A., Kallman R. F. A new mouse tumor model system (RIF-1) for comparison of end-point studies. J Natl Cancer Inst. 1980 Mar;64(3):595–604. [PubMed] [Google Scholar]
  17. Vaupel P., Okunieff P., Kallinowski F., Neuringer L. J. Correlations between 31P-NMR spectroscopy and tissue O2 tension measurements in a murine fibrosarcoma. Radiat Res. 1989 Dec;120(3):477–493. [PubMed] [Google Scholar]
  18. Voorhees W. D., 3rd, Babbs C. F. Hydralazine-enhanced selective heating of transmissible venereal tumor implants in dogs. Eur J Cancer Clin Oncol. 1982 Oct;18(10):1027–1033. doi: 10.1016/0277-5379(82)90252-8. [DOI] [PubMed] [Google Scholar]
  19. Wood P. J., Hirst D. G. Cinnarizine and flunarizine as radiation sensitisers in two murine tumours. Br J Cancer. 1988 Dec;58(6):742–745. doi: 10.1038/bjc.1988.301. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES