RADIATION DOSE-DEPENDENT CHANGES IN TUMOR METABOLISM MEASURED BY P-31NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

The effects of radiation dose upon a hypoxic murine mammary carcinoma were followed using P-31 nuclear magnetic resonance spectroscopy. Anim als were studied before and over the course of 9 days after tumors wer e irradiated with a single dose of 0, 4, 8, or 17 Gy. The current data is compared to our previous studies of the effects of 32 or 65 Gy on the same tumor model. The energy status of the tumors, as reflected in nucleotide triphosphate:Pi and phosphocreatine:Pi ratios, improved af ter receiving a dose of 8 to 65 Gy and decreased after receiving 0 or 4 Gy doses. The energy status of the 8- to 65-Gy dose cohorts reached a maximum between 1 and 4 days after irradiation. Additionally, the ch ange in the hypoxic cell fraction 48 h after a 17-Gy dose was determin ed; it was calculated from changes in the doses required to control 50 % of the tumors post radiation for clamped (hypoxic) and unclamped (no rmoxic) tumors in parallel animal cohorts. A significant decrease comp ared to preirradiation values was observed in the hypoxic cell fractio n following 17 Gy irradiation. This decrease was temporally coincident with increases in tumor energy status measured using nuclear magnetic resonance and was similar to our previously reported results of the c hange in hypoxic fraction 48 h after a 32-Gy dose. Changes in the rela tive ratio of phosphomonoesters showed a strong dose dependence after irradiation. The downfield component of the phosphomonoester peak, whi ch consists largely of phosphoethanolamine, increased relative to the upfield component, phosphocholine. This dose-dependent ratio reached a maximum approximately 7 days post radiation. Changes in the levels of membrane phospholipid precursors may be related to alterations in cel l proliferation or may be a result of radiation-induced membrane damag e.