P-31 NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY, HISTOLOGY AND CYTOKINETICS OF A XENOGRAFTED HYPOPHARYNX CARCINOMA FOLLOWING TREATMENT WITH CISPLATIN - COMPARISON IN 3 SUBLINES WITH INCREASING RESISTANCE

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 P-31 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, paralleled 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 P-31 NMR spectrum which were similar to those observed during uninfluenced tumour growth. Marked changes in the P-31 NMR spectrum were always associated with severe cytotoxic lesions following therapy. The results suggest that the changes detected by P-31 NMR spectroscopy following chemotherapy with CDDP are response-specific.