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. 1991 Sep;64(3):485–493. doi: 10.1038/bjc.1991.336

31P nuclear magnetic resonance spectroscopy, histology and cytokinetics of a xenografted hypopharynx carcinoma following treatment with cisplatin: comparison in three sublines with increasing resistance.

R Tausch-Treml 1, P Köpf-Maier 1, F Baumgart 1, B Gewiese 1, D Ziessow 1, H Scherer 1, K J Wolf 1
PMCID: PMC1977659  PMID: 1911189

Abstract

The changes in the phosphorus metabolism of a xenografted hypopharynx carcinoma (Hyp 1), sensitive to cisplatin (CDDP), were compared to those occurring in two sublines of the tumour, characterised by moderate or high resistance to CDDP (Hyp 1/H and Hyp 1/R) following, i.p. administration of 4, 8 or 12 mg CDDP/kg-1. The investigations were performed by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Parallel to the NMR experiments, the cytokinetic and histological alterations in the tumours were studied under the same experimental conditions. No mentionable differences in the levels of the main phosphorus-containing metabolites could be detected between the three tumour lines before treatment. Following application of CDDP, the alterations in the NMR spectra were clearly related to the degree of tumour response. The most sensitive and earliest marker of tumour regression was a decrease in the phosphomonoester/phosphodiester ratio, parallelled by a gradual increase in the phosphocreatine/inorganic phosphorus quotient. In the resistant tumour lines Hyp 1/H and Hyp 1/R non-responding tumours showed alterations in the 31P NMR spectrum which were similar to those observed during uninfluenced tumour growth. Marked changes in the 31P NMR spectrum were always associated with severe cytotoxic lesions following therapy. The results suggest that the changes detected by 31P NMR spectroscopy following chemotherapy with CDDP are response-specific.

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Selected References

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

  1. Cohen J. S., Lyon R. C., Chen C., Faustino P. J., Batist G., Shoemaker M., Rubalcaba E., Cowan K. H. Differences in phosphate metabolite levels in drug-sensitive and -resistant human breast cancer cell lines determined by 31P magnetic resonance spectroscopy. Cancer Res. 1986 Aug;46(8):4087–4090. [PubMed] [Google Scholar]
  2. Cohen J. S. Phospholipid and energy metabolism of cancer cells monitored by 31P magnetic resonance spectroscopy: possible clinical significance. Mayo Clin Proc. 1988 Dec;63(12):1199–1207. doi: 10.1016/s0025-6196(12)65406-8. [DOI] [PubMed] [Google Scholar]
  3. Daly P. F., Zugmaier G., Sandler D., Carpen M., Myers C. E., Cohen J. S. Regulation of the cytidine phospholipid pathways in human cancer cells and effects of 1-beta-D-arabinofuranosylcytosine: a noninvasive 31P nuclear magnetic resonance study. Cancer Res. 1990 Feb 1;50(3):552–557. [PubMed] [Google Scholar]
  4. Eastman A., Schulte N. Enhanced DNA repair as a mechanism of resistance to cis-diamminedichloroplatinum(II). Biochemistry. 1988 Jun 28;27(13):4730–4734. doi: 10.1021/bi00413a022. [DOI] [PubMed] [Google Scholar]
  5. Evelhoch J. L., Keller N. A., Corbett T. H. Response-specific adriamycin sensitivity markers provided by in vivo 31P nuclear magnetic resonance spectroscopy in murine mammary adenocarcinomas. Cancer Res. 1987 Jul 1;47(13):3396–3401. [PubMed] [Google Scholar]
  6. 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]
  7. Glickson J. D. Clinical NMR spectroscopy of tumors. Current status and future directions. Invest Radiol. 1989 Dec;24(12):1011–1016. doi: 10.1097/00004424-198912000-00020. [DOI] [PubMed] [Google Scholar]
  8. Lyon R. C., Cohen J. S., Faustino P. J., Megnin F., Myers C. E. Glucose metabolism in drug-sensitive and drug-resistant human breast cancer cells monitored by magnetic resonance spectroscopy. Cancer Res. 1988 Feb 15;48(4):870–877. [PubMed] [Google Scholar]
  9. Maris J. M., Evans A. E., McLaughlin A. C., D'Angio G. J., Bolinger L., Manos H., Chance B. 31P nuclear magnetic resonance spectroscopic investigation of human neuroblastoma in situ. N Engl J Med. 1985 Jun 6;312(23):1500–1505. doi: 10.1056/NEJM198506063122307. [DOI] [PubMed] [Google Scholar]
  10. Masuda H., Ozols R. F., Lai G. M., Fojo A., Rothenberg M., Hamilton T. C. Increased DNA repair as a mechanism of acquired resistance to cis-diamminedichloroplatinum (II) in human ovarian cancer cell lines. Cancer Res. 1988 Oct 15;48(20):5713–5716. [PubMed] [Google Scholar]
  11. Sekiya S., Oosaki T., Andoh S., Suzuki N., Akaboshi M., Takamizawa H. Mechanisms of resistance to cis-diamminedichloroplatinum (II) in a rat ovarian carcinoma cell line. Eur J Cancer Clin Oncol. 1989 Mar;25(3):429–437. doi: 10.1016/0277-5379(89)90255-1. [DOI] [PubMed] [Google Scholar]
  12. Seo Y., Murakami M., Watari H., Imai Y., Yoshizaki K., Nishikawa H., Morimoto T. Intracellular pH determination by a 31P-NMR technique. The second dissociation constant of phosphoric acid in a biological system. J Biochem. 1983 Sep;94(3):729–734. doi: 10.1093/oxfordjournals.jbchem.a134413. [DOI] [PubMed] [Google Scholar]
  13. Sostman D., Rockwell S., Smith G. J., Gore J. C., Kennedy K. A., Habib A., Fischer J. J., Armitage I. M., Holcomb W. Magnetic resonance, pathology and physiology of the BA1112 rhabdomyosarcoma in vivo. Invest Radiol. 1988 Apr;23(4):277–288. doi: 10.1097/00004424-198804000-00007. [DOI] [PubMed] [Google Scholar]
  14. Steen R. G. Response of solid tumors to chemotherapy monitored by in vivo 31P nuclear magnetic resonance spectroscopy: a review. Cancer Res. 1989 Aug 1;49(15):4075–4085. [PubMed] [Google Scholar]
  15. Toohill R. J., Anderson T., Byhardt R. W., Cox J. D., Duncavage J. A., Grossman T. W., Haas C. D., Haas J. S., Hartz A. J., Libnoch J. A. Cisplatin and fluorouracil as neoadjuvant therapy in head and neck cancer. A preliminary report. Arch Otolaryngol Head Neck Surg. 1987 Jul;113(7):758–761. doi: 10.1001/archotol.1987.01860070072019. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. van den Bosch H. Phosphoglyceride metabolism. Annu Rev Biochem. 1974;43(0):243–277. doi: 10.1146/annurev.bi.43.070174.001331. [DOI] [PubMed] [Google Scholar]

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