Sorokina L. The functioning of mitochondria of the cells of experimental tumors in the growth kinetics and under influence of sodium dichloroacetate

Dissertation is devoted to the study of energy metabolism and oxidative processes in sarcoma 37 (S37) and Lewis lung carcinoma (LLC) in the growth kinetics in vivo and under influence of sodium dichloroacetate (SDA). The retardation of S37 (but not LLC) growth is observed under influence of the compound. The intensity of lipid peroxidation (LP) was increased in S37 together with the decrease of antioxidant enzymes (AO) activity with tumor growth. The SDA administration leads to the additional enhancement of the oxidative processes, particularly in the mitochondrial membranes (MM) and to the insufficient functioning of AO in S37. Under SDA influence the activity of pyruvate dehydrogenase was increased, the lactate content decreased, and the activities of respiratory chain and the content of cytochromes were also reduced in S37. The changes of the conformational state of the proteins in MM and the increase of lipid phase microviscosity of MM were shown under the action of SDA. The observed changes were not characteristic for LLC tumors of SDA-treated mice. Thus, under the treatment with SDA the cytotoxic effect of ROS excess formed through the generation of oxygen radicals by the respiratory chain complexes in the conditions of the reduced AO activity could be realized. The insensitivity of LLC to the influence of SDA is possibly caused with the insufficient level of pyruvate dehydrogenase activation in LLC or with the higher compared with S37 efficacy of the AO system functioning in LLC.