ESR and31P NMR study of metabolic changes in mouse tumor and liver after combined misonidazole and irradiation treatment

Abstract

A combination of ESR and 3tp NMR techniques was used to study the mechanism of the radiosensitizing influence of misonidazole (MISO) on mouse tumors and liver. The MISO injection (1 g/kg) was shown to cause signi¡ metabolic changes in tumors, such as ah increase in the content of nitrosyl complexes, increases in adenosine diphosphate and inorganic phosphate levels, and decreases in phosphomonoesters, phosphodiesters, adenosine triphosphate and phosphocreatine in the initial period of observation. These alterations were accompanied by slight cytosol alkalinization (pH shift ca 0.15). A decrease in the ESR signal intensity of MoS+-containing enzymes, an increase in the cytochrome P-450 signal anda significant increase in the free radical signal were observed in liver after MISO treatment. Local irradiaª of tumors (30 Gy) 30 min after MISO injection led to the enhancement and prolongation of nearly all the effects induced by MISO treatment. The combined effect of MISO and irradiation was not simply the sum of their separate effects. It is suggested that radiation enhances cytotoxic effects of nitrocompounds on hypoxic tumor cells, intª glycolysis and inducing greater production of toxic and highly reactive intermediates resulting from incomplete nitro group reduction. The latter appears to be considered as the major factor involved in the radiosensitizing action of nitrocompounds.