Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Apr;69(4):633–640. doi: 10.1038/bjc.1994.124

Phosphorus metabolism during growth of lymphoma in mouse liver: a comparison of 31P magnetic resonance spectroscopy in vivo and in vitro.

C P Thomas 1, R M Dixon 1, M Tian 1, S A Butler 1, C J Counsell 1, J K Bradley 1, G E Adams 1, G K Radda 1
PMCID: PMC1968832  PMID: 8142251

Abstract

Large phosphomonoester (PME) signals are detected in the phosphorus magnetic resonance spectra (31P MRS) of many neoplastic and rapidly dividing tissues. In addition, alterations in phosphodiester (PDE) signals are sometimes seen. The present study of a murine lymphoma growing in liver showed a positive correlation between the hepatic PME/PDE ratio measured in vivo by 31P MRS at 4.7 T and the degree of lymphomatous infiltration in the liver, quantified by histology. High-resolution 31P MRS of liver extracts at 9.7 T showed that the PME peak consists largely of phosphoethanolamine (PE) and to a lesser extent of phosphocholine (PC). The concentration of both PE and PC increased positively with lymphomatous infiltration of the liver. In vivo, the PDE peak contains signals from phospholipids (mostly phosphatidylethanolamine and phosphatidylcholine) and the phospholipid breakdown products glycerophosphoethanolamine (GPE) and glycerophosphocholine (GPC). Low levels of GPE and GPC were detected in the aqueous extracts of the control and infiltrated livers; their concentrations remained unchanged as the infiltration increased. The total concentration of phospholipids measured by 31P MRS of organic extracts decreased about 3-fold as the infiltration increased to 70%. Thus, our data showed that the increased PME/PDE ratio in vivo is due to both an increase in the PME metabolites and a decrease in the PDE metabolites. We propose that this ratio can be used as a non-invasive measure of the degree of lymphomatous infiltration in vivo.

Full text

PDF
633

Images in this article

636Figure 2
on p.636

Selected References

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

  1. Adams G. E., Bremner J. C., Counsell C. J., Stratford I. J., Thomas C., Wood P. J. Magnetic resonance spectroscopy studies on experimental murine and human tumors: comparison of changes in phosphorus metabolism with induced changes in vascular volume. Int J Radiat Oncol Biol Phys. 1992;22(3):467–471. doi: 10.1016/0360-3016(92)90855-c. [DOI] [PubMed] [Google Scholar]
  2. Allavena C., Guerquin-Kern J. L., Lhoste J. M. Follow-up by 31P NMR spectroscopy of the energy metabolism of malignant tumor in rats during treatment. Radiother Oncol. 1991 May;21(1):48–52. doi: 10.1016/0167-8140(91)90340-m. [DOI] [PubMed] [Google Scholar]
  3. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  4. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brosnan M. J., Chen L., Van Dyke T. A., Koretsky A. P. Free ADP levels in transgenic mouse liver expressing creatine kinase. Effects of enzyme activity, phosphagen type, and substrate concentration. J Biol Chem. 1990 Dec 5;265(34):20849–20855. [PubMed] [Google Scholar]
  6. Cobb L. M., Butler S. A. The influence of prior total body irradiation on the tissue distribution of mouse lymphoma/leukemia. Int J Radiat Oncol Biol Phys. 1986 Jan;12(1):83–88. doi: 10.1016/0360-3016(86)90419-0. [DOI] [PubMed] [Google Scholar]
  7. Cox I. J., Coutts G. A., Gadian D. G., Ghosh P., Sargentoni J., Young I. R. Saturation effects in phosphorus-31 magnetic resonance spectra of the human liver. Magn Reson Med. 1991 Jan;17(1):53–61. doi: 10.1002/mrm.1910170110. [DOI] [PubMed] [Google Scholar]
  8. Daly P. F., Cohen J. S. Magnetic resonance spectroscopy of tumors and potential in vivo clinical applications: a review. Cancer Res. 1989 Feb 15;49(4):770–779. [PubMed] [Google Scholar]
  9. Daly P. F., Lyon R. C., Faustino P. J., Cohen J. S. Phospholipid metabolism in cancer cells monitored by 31P NMR spectroscopy. J Biol Chem. 1987 Nov 5;262(31):14875–14878. [PubMed] [Google Scholar]
  10. Dixon R. M., Angus P. W., Rajagopalan B., Radda G. K. Abnormal phosphomonoester signals in 31P MR spectra from patients with hepatic lymphoma. A possible marker of liver infiltration and response to chemotherapy. Br J Cancer. 1991 Jun;63(6):953–958. doi: 10.1038/bjc.1991.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dixon R. M., Tian M. Phospholipid synthesis in the lymphomatous mouse liver studied by 31P nuclear magnetic resonance spectroscopy in vitro and by administration of 14C-radiolabelled compounds in vivo. Biochim Biophys Acta. 1993 Apr 30;1181(2):111–121. doi: 10.1016/0925-4439(93)90099-m. [DOI] [PubMed] [Google Scholar]
  12. Dunn J. F., Kemp G. J., Radda G. K. Depth selective quantification of phosphorus metabolites in human calf muscle. NMR Biomed. 1992 May-Jun;5(3):154–160. doi: 10.1002/nbm.1940050309. [DOI] [PubMed] [Google Scholar]
  13. Exton J. H. Signaling through phosphatidylcholine breakdown. J Biol Chem. 1990 Jan 5;265(1):1–4. [PubMed] [Google Scholar]
  14. Freyer J. P., Schor P. L., Jarrett K. A., Neeman M., Sillerud L. O. Cellular energetics measured by phosphorous nuclear magnetic resonance spectroscopy are not correlated with chronic nutrient deficiency in multicellular tumor spheroids. Cancer Res. 1991 Aug 1;51(15):3831–3837. [PubMed] [Google Scholar]
  15. Houweling M., Tijburg L. B., Jamil H., Vance D. E., Nyathi C. B., Vaartjes W. J., van Golde L. M. Phosphatidylcholine metabolism in rat liver after partial hepatectomy. Evidence for increased activity and amount of CTP:phosphocholine cytidylyltransferase. Biochem J. 1991 Sep 1;278(Pt 2):347–351. doi: 10.1042/bj2780347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Houweling M., Tijburg L. B., Vaartjes W. J., van Golde L. M. Phosphatidylethanolamine metabolism in rat liver after partial hepatectomy. Control of biosynthesis of phosphatidylethanolamine by the availability of ethanolamine. Biochem J. 1992 Apr 1;283(Pt 1):55–61. doi: 10.1042/bj2830055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. KENNEDY E. P., WEISS S. B. The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem. 1956 Sep;222(1):193–214. [PubMed] [Google Scholar]
  18. Moon R. B., Richards J. H. Determination of intracellular pH by 31P magnetic resonance. J Biol Chem. 1973 Oct 25;248(20):7276–7278. [PubMed] [Google Scholar]
  19. Murphy E. J., Brindle K. M., Rorison C. J., Dixon R. M., Rajagopalan B., Radda G. K. Changes in phosphatidylethanolamine metabolism in regenerating rat liver as measured by 31P-NMR. Biochim Biophys Acta. 1992 Apr 30;1135(1):27–34. doi: 10.1016/0167-4889(92)90162-5. [DOI] [PubMed] [Google Scholar]
  20. Murphy E. J., Rajagopalan B., Brindle K. M., Radda G. K. Phospholipid bilayer contribution to 31P NMR spectra in vivo. Magn Reson Med. 1989 Nov;12(2):282–289. doi: 10.1002/mrm.1910120218. [DOI] [PubMed] [Google Scholar]
  21. Oberhaensli R. D., Galloway G. J., Hilton-Jones D., Bore P. J., Styles P., Rajagopalan B., Taylor D. J., Radda G. K. The study of human organs by phosphorus-31 topical magnetic resonance spectroscopy. Br J Radiol. 1987 Apr;60(712):367–373. doi: 10.1259/0007-1285-60-712-367. [DOI] [PubMed] [Google Scholar]
  22. Okunieff P. G., Koutcher J. A., Gerweck L., McFarland E., Hitzig B., Urano M., Brady T., Neuringer L., Suit H. D. Tumor size dependent changes in a murine fibrosarcoma: use of in vivo 31P NMR for non-invasive evaluation of tumor metabolic status. Int J Radiat Oncol Biol Phys. 1986 May;12(5):793–799. doi: 10.1016/0360-3016(86)90038-6. [DOI] [PubMed] [Google Scholar]
  23. Ronen S. M., Stier A., Degani H. NMR studies of the lipid metabolism of T47D human breast cancer spheroids. FEBS Lett. 1990 Jun 18;266(1-2):147–149. doi: 10.1016/0014-5793(90)81526-t. [DOI] [PubMed] [Google Scholar]
  24. Smith T. A., Glaholm J., Leach M. O., Machin L., Collins D. J., Payne G. S., McCready V. R. A comparison of in vivo and in vitro 31P NMR spectra from human breast tumours: variations in phospholipid metabolism. Br J Cancer. 1991 Apr;63(4):514–516. doi: 10.1038/bjc.1991.122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Taylor D. J., Styles P., Matthews P. M., Arnold D. A., Gadian D. G., Bore P., Radda G. K. Energetics of human muscle: exercise-induced ATP depletion. Magn Reson Med. 1986 Feb;3(1):44–54. doi: 10.1002/mrm.1910030107. [DOI] [PubMed] [Google Scholar]
  26. Van der Grond J., Dijkstra G., Roelofsen B., Mali W. P. 31P-NMR determination of phosphomonoesters in relation to phospholipid biosynthesis in testis of the rat at different ages. Biochim Biophys Acta. 1991 May 24;1074(1):189–194. doi: 10.1016/0304-4165(91)90060-t. [DOI] [PubMed] [Google Scholar]
  27. Veech R. L., Lawson J. W., Cornell N. W., Krebs H. A. Cytosolic phosphorylation potential. J Biol Chem. 1979 Jul 25;254(14):6538–6547. [PubMed] [Google Scholar]

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

RESOURCES