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The effect of indralin on the metabolic parameters in peripheral blood and organs of irradiated dogs and mice have been studied by EPR, NMR and radioisotope methods. It has been shown that indralin stimulated biosynthesis of DNA precursors as well as of DNA and proteins in the organs and stabilized the rate of ATP and glycogen synthesis. As a result indralin reduced considerably the changes produced by gamma-irradiation on the macromolecular biosynthesis during the early post-irradiation period. Indralin has induced marked favorable changes in the rate of macromolecular synthesis, normalized the ATP and glycogen content, induced ribonucleotide reductase activity and increased the Fe(3+)-transferrin content during development of compensatory-repair response in the irradiated animals. Indralin prevented hyperdevelopment of the repair response and its breakdown due to radiation-induced exhaustion of viability of many important cellular and body systems after irradiation with lethal doses.

31P NMR was used to study the systemic effects of a tumor on a host organism by monitoring the phosphate metabolite content in freshly excised mouse liver at 0-4 degrees C and in ethanolic liver extracts of animals suffering from La, L1210 and P388 leukemias and Ehrlich ascites tumor (EAT). The progression of murine leukemia is characterized by increases in the intensities of the resonances of Pi and phosphomonoesters (PME), in particular, phosphorylethanolamine, in liver; phosphodiester (PDE) signals increase two- to four-fold during the period of rapid tumor growth and decline to undetectable levels in the terminal stage. There were no reliable alterations detected in the ATP content and intracellular pH throughout the course of the leukemia. The kinetics of intracellular phosphates are similar in various kinds of leukemia but quite different in EAT. The reduction of inoculum causes the appearance of maxima in the Pi and PME profiles in the latent period of La leukemia, but the profiles of liver PDE considered from the end of the latent period are independent of inoculum. Possible mechanisms for the changes in PDE concentrations and their biochemical role are discussed. NMR spectroscopy of liver may be used to indirectly monitor the progression of tumors unavailable for direct NMR assay.

In order to study the effects of epinephrine and insulin on liver metabolism, measurements of cellular phosphates and intracellular pH by 31PNMR, of glycogen by 13C NMR and of lactate by 1H NMR were performed in freshly dissected mouse liver at 0-4 degrees C and in ethanolic liver extracts. The injection of epinephrine hydrochloride (0.1 mL of 0.1% solution i.p. per mouse) caused remarkable changes in liver metabolic profiles which were expressed most distinctly in 15-30 min and could not be attributed solely to epinephrine-induced hyperglycemia. Among these metabolic changes are falls in the levels of ATP and uridine diphosphate sugars by 60-70%, possibly related to glycogen depletion, and intracellular acidification by 0.5 units attributed to the release of protons during hydrolysis of ATP rather than to accumulation of lactate in anaerobic glycolysis. Insulin injected prior to epinephrine (4 units i.p.) markedly suppressed epinephrine-induced metabolic alterations, although the effect of the combination of insulin and epinephrine was not the sum of the separate effects of these hormones. The maximum protective effect of insulin was reached when insulin was injected 15 min prior to epinephrine. The results obtained demonstrate the applicability of NMR for evaluating the protective activity of modifiers at various extreme exposures.