IN-VITRO AND IN-VIVO P-31 NUCLEAR-MAGNETIC-RESONANCE MEASUREMENTS OF METABOLIC CHANGES POST RADIATION

Radiation-induced metabolic changes previously observed in tumors usin g phosphorus nuclear magnetic resonance spectroscopy include changes i n the relative amounts of the phospholipid precursors phosphoethanolam ine and phosphocholine, increases in membrane catabolites, and increas es in energy status. To elucidate the degree to which these in vivo al terations are a result of intrinsic cellular changes versus radiation- induced systemic effects, the Radiation-Induced Fibrosarcoma-1 tumor m odel was studied before and over the course of 7 days after a single d ose of 17 Gy. In vivo studies were performed with tumors implanted in C3H/He mice; in vitro studies used cells that were perfused in agarose gel threads after being grown, radiated, and maintained in monolayer. The statistically significant increases in the downfield component of the phosphomonoester peak, which consists primarily of phosphoethanol amine, compared to the upfield component, phosphocholine, were qualita tively similar in vivo and in vitro post radiation. Statistically sign ificant increases in the membrane catabolite glycerophosphocholine, a phosphodiester, were also observed in both tumors and cell culture aft er irradiation, with a greater percentage change in vitro. This sugges ts that changes in the phosphomonoester and phosphodiester concentrati ons are primarily an intrinsic effect of radiation on cellular metabol ism, modulated to a lesser degree by systemic effects. In contrast, th e statistically significant increases in energy status after the 17-Gy dose showed markedly different temporal responses in the two systems. Therefore, energy status changes observed in vivo are due largely to systemic changes, such as changes in blood flow. Flow cgtometry data o btained from the cultured cells showed a sustained increase in the G(2 )-M fraction starting at 21 h, the first time point measured after irr adiation, which continued for the 7 days studied post radiation. These data indicate that the in vivo changes detected by nuclear magnetic r esonance in phospholipid precursors and catabolites occur directly at the cellular level and may reflect cell death or growth inhibition aft er antineoplastic therapy.