31P NMR spectroscopy of a xenografted hypopharynx carcinoma: effects of tumor growth and treatment with cisplatin on the tumor phosphorus metabolism, histology and cytokinetics.

A xenografted hypopharynx carcinoma growing subcutaneously in nude mice was studied by in vivo 31P NMR spectroscopy during uninfluenced growth and following treatment with cisplatin (CDDP). Parallel to the NMR experiments, the cytokinetic and histological changes in the tumor were investigated. The most significant change in the growing tumor was a decline in the level of phosphocreatine (PCr), whereas the tumor pH did not change. Following treatment with CDDP (4, 8 and 12 mg/kg), a dose-dependent decrease in the level of phosphomonoesters (PME) took place, whilst no dose dependence could be observed for the increase of PCr. the pH shifted to alkaline only after administration of the highest CDDP dose. Tumor cytokinetics revealed a cell arrest at the G1/S boundary 24 h after chemotherapy. At this time, the histological sections showed a dilatation of capillaries, whereas first necroses appeared on day 3. The proliferative activity of the tumor showed a sharp decline 24 h after CDDP application, followed by a revival of cell proliferation that was proportional to the dose applied between days 5 and 7. This increase in proliferative activity was paralleled by a marked increase in the PME/phosphodiesters ratio. Thus, in the tumor investigated the PME were the best indicators of tumor response to therapy. A precise correlation between the cytokinetic data and the re-energization of the tumor was not possible because histological changes, which may contribute to improved tumor energy status took place at the same time.