Imbalance in the enzymatic system of production and consumption of active oxygen species in liver of AKR mice with spontaneous leucosis

Activities of protective antioxidant enzymes, the rate of superoxide formation (v) in microsomal membranes and submitochondrial particles (SMP), and the concentrations of reduced and oxidized glutathione in cytosol were studied in the liver of AKR mice during the development of spontaneous leucosis. It was found that in the latent period of leucosis (mice of 3-6 months of age) the glutathione reductase (GR) activity in cytosol and mitochondria decreased and v in SMP increased. The increase in v in SMP did not result in the induction of Mn-SOD. In this stage of leucosis, the activities of Cu,Zn-SOD, GSH-Px, and G-6-PDH in cytosol were unchanged; at the same time, the GR activity and the concentration of reduced glutathione smoothly decreased. In the stage of developed leucosis (mice of 7-9 months of age), non-synchronous changes in the antioxidant system resulting in the shift of metabolism towards the prooxidant state were found. Comparison of our findings and the literature data demonstrates that the observed decrease in the SOD/GSH-Px ratio, the decrease in GR activity, and the increase in the v/Mn-SOD activity ratio are typical for pre-neoplastic changes in cell metabolism.