P-31 NMR-SPECTROSCOPY STUDIES OF PHOSPHOLIPID-METABOLISM IN HUMAN-MELANOMA XENOGRAFT LINES DIFFERING IN RATE OF TUMOR-CELL PROLIFERATION

The concentration of phospholipid metabolites in tumours has been hypo thesized to be related to rate of cell membrane turnover and may refle ct rate of cell proliferation. The purpose of the study reported here was to investigate whether P-31 NMR resonance ratios involving the pho sphomonoester (PME) or phosphodiester (PDE) resonance are correlated t o fraction of cells in S-phase or volume-doubling time in experimental tumours, Four human melanoma xenograft lines (BEX-t, HUX-t, SAX-t, WI X-t) were included in the study, The tumours were grown subcutaneously in male BALB/c-nu/nu mice, P-31 NMR spectroscopy was performed at a m agnetic field strength of 4.7 T, Fraction of cells in S-phase was meas ured by flow cytometry, Tumour volume-doubling time was determined by Gompertzian analysis of volumetric growth data, BEX-t and SAX-t tumour s differed in fraction of cells in S-phase and volume-doubling time, b ut showed similar P-31 NMR resonance ratios, BEX-t and WIX-t tumours s howed significantly different P-31 NMR resonance ratios but similar fr actions of cells in S-phase. The P-31 NMR resonance ratios were signif icantly different for small and large HUX-t tumours even though fracti on of cells in S-phase and volume-doubling time did not differ with tu mour volume, None of the P-31 NMR resonance ratios showed significant increase with increasing fraction of cells in S-phase or significant d ecrease with increasing tumour volume-doubling time across the four xe nograft lines. Consequently, the PME and PDE resonances of P-31 NMR sp ectra recorded in vivo are probably of limited value in assessment of rate of fell proliferation in tumours and hence also in prediction of tumour treatment resistance caused by rapid cell proliferation.