31P magnetic resonance spectroscopy of human colon cancer

Abstract

Phosphatic metabolite profiles of 19 malignant and normal human colon specimens were analyzed by techniques of perchloric acid extraction and 31P magnetic resonance spectroscopy at 202.4 MHz. Thirty-one individual phosphorus-containing intermediates of metabolism were identified and quantified for statistical intergroup comparisons. Elevations in relative concentrations of phosphorylethanolamine, IMP, NADP 2'-P, an uncharacterized resonance at 3.72 delta, glycerol 3-phosphorylcholine, phosphorylated glycans and the nucleoside diphosphosugars were seen in malignant tissues concurrently with reductions in relative concentrations of phosphorylcholine, phosphocreatine (PCr), and ATP. The malignant and normal tissue groups were further characterized and contrasted by computing metabolic indices from spectral data. Significant elevations in phosphomonoesters, glycerolphosphodiesters, the ratio of phosphorylethanolamine/phosphorylcholine, and phosphomonoesters/inorganic orthophosphate were detected in malignant tissues along with significant reductions in the ratios of PCr/inorganic orthophosphate, PCr/ATP, the energy charge of the adenylate system and the tissue energy modulus. These results revealed significant alterations in high energy metabolism, low energy metabolism, and membrane metabolism characteristic of malignant tissues. The reduction in high energy phosphates ATP and PCr was balanced by the net increase in nucleoside diphosphosugar and a shift in equilibrium to metabolism involving low energy phosphomonoesters. The spectral data of the tumors, which were of epithelial origin, demonstrated minor metabolites not previously detected in tissue extract analysis of malignant tissues. Detection of these minor metabolites represents an indirect measurement of phospholipid metabolism in malignant tissues.