PHOSPHORUS METABOLITE CHARACTERIZATION OF HUMAN PROSTATIC ADENOCARCINOMA IN A NUDE-MOUSE MODEL BY P-31 MAGNETIC-RESONANCE SPECTROSCOPY AND HIGH-PRESSURE LIQUID-CHROMATOGRAPHY

A series of experiments were conducted to identify and quantify the phosphorus metabolites of DU 145 xenografts (a human prostatic adenocarcinoma cell line grown in nude mice) using P-31 MRS and HPLC. The P-31 spectral characteristics of DU 145 xenografts were compared to perfused DU 145 cells and to in situ human prostatic adenocarcinomas. These studies demonstrated that both DU 145 xenografts and perfused DU 145 cells exhibited reduced levels of phosphocreatine relative to spectra of in situ human prostatic adenocarcinomas. Elevated levels of phosphomonesters (PMEs) were observed in P-31 spectra of both DU 145 xenografts and in situ human prostatic adenocarcinomas. The major components of the PME resonance of DU 145 xenografts were identified as phosphocholine and phosphoethanolamine. High levels of diphosphodiesters (DPDEs) were consistently observed for both DU 145 xenografts and perfused DU 145 cells, but were absent in P-31 spectra of in situ primary human adenocarcinomas. In agreement with spectroscopic results, high pressure liquid chromatographic analyses of human tissue removed at surgery contained insignificant amounts of DPDEs while DU 145 xenografts had high levels of DPDEs consisting mainly of uridine-5'-diphospho-N-acetylgalactosamine (22.4 nmol/mg protein) and uridine-5'-diphospho-N-acetylglucosamine (7.4 nmol/mg protein).