[REPROGRAMMING OF MITOCHONDRIAL ENERGY METABOLISM IN MALIGNANT NEOPLASMS].

The novel ideas of fundamental role of mitochondria in the maintenance of viability of malignant cells have been reviewed. The modern state of research is considered in detail, including: mitochondrial control of the cellular redox state, sites of reactive oxygen species (ROS) production in inner mitochondrial membrane and antioxidant protection systems. Specificities of the structural-functional mitochondrial remodelling in malignant tumors, the mechanisms of the energy metabolism reprogramming, enhancement of the ROS production and adaptation to the hypoxic conditions and metabolic stress are analyzed. The available data including our research on transplanted tumors indicate that cytotoxic action of sodium dichloroacetate (the inhibitor of pyruvate dehydrogenase kinase) depends on biological properties of tumors and intensity of structural-functional mitochondrial rearrangement. Dichloroacetate turned out to be effective for sarcoma 37, but not for Lewis lung carcinoma.

The influence of sodium dichloroacetate on the oxidative processes in sarcoma 37.

AIM: to study the activity of antioxidant enzymes and to evaluate an intensity of prooxidant processes in sarcoma 37 (S37) cells during tumor development and under influence of sodium dichloroacetate (SDA). METHODS: Activity of total superoxide dismutase (SOD), SOD isoforms, catalase (Cat), glutathione peroxidase (GP), and glutathione reductase (GR), as well as content of reduced glutathione (GSH) and lipid peroxidation (LP) secondary byproducts were determined in S37 homogenated tissues of untreated mice and animals treated with SDA at daily dose of 86 mg/kg. RESULTS: SDA treatment of S37-bearing mice resulted in the reduced activities of total SOD, SOD isoforms (especially Mn-SOD), Cat, GP and significantly decreased GSH content on the background of LP intensification in tumor tissue. CONCLUSION: The observed changes of oxidative homeostasis in S37-bearing animals treated with SDA could be considered as an element of antitumor action of SDA.

[Effect of metronidazole and local irradiation of the tumor on paramagnetic metal complexes of the liver and tumor tissues]. / Vliianie metronidazola i lokal'nogo oblucheniia opukholi na paramagnitnye metallokompleksy tkanei pecheni i opukholi.

A study was made of changes in the intensity of the ESR signals in tissues of sarcoma-37 and liver of mice after radiation of the tumor, administration of metronidazole, and after the combined effect of the two factors. The most pronounced changes in the ESR signals were induced by metronidazole. An appreciable increase in the content of nitrosyl complexes in the tumor was noted after the combined effect of metronidazole and radiation which was indicative of the radiation-induced formation of a large number of metronidazole anion-radicals in the tumor.

[Potentiating effect of disodium salt of 2,6-dimethyl-1,4-dihydropyridine-3,5-bis-carbonyl hydroxyacetic acid on the activity of various antitumor agents]. / Potentsiiruiushchee deistvie dinatrievoi soli 2,6-dimetil-1,4-digidropiridin-3,5-bis-karboniloksiuksusnoi kisloty na aktivnost' nekotorykh protivoopukholevykh preparatov.

The disodium salt of 2,6-dimethyl-1,4-dihydropyridine-3,5-bis-carbonyl hydroxyacetic acid (I) used in the mg/kg dose decreases the cyclophosphane toxicity in mice and potentiates the cytostatic activity of cyclophosphane, 5-fluorouracil and arabinosyl cytosine against leukemia P388, murine sarcoma 37 and Walker's carcinosarcoma. Administered alone I exhibits no antitumour activity. The potentiation of the antitumour effect of drugs appears independent of the administration schedule. Biochemical evidence indicates that I does not block DNA synthesis in leukemic cells in vitro, but significantly enhances the DNA-blocking effect of cyclophosphane in the same cells in vivo.

[Disordered DNA repair in tumor cells as affected by sarcolysine]. / Narushenie reparatsii DNK opukholevykh kletok pod deistviem sarkolizina.

Sarcolysine-induced damaging and reparative processes in the primary structure of tumour cell DNA have been studied. The presence of low sarcolysine concentrations (1 mkM) in the cell culture during the first two hours of incubation caused suturing of DNA molecules. The increase of the incubation time from 4 to 18 hours and the rise in the drug concentration (by 10.20 times and more) resulted in intensive accumulation of one-strand breaks. However, we have not observed the appearance of high-molecular DNA, which is the evidence of the completion of the reparative process. The impulse treatment with sarcolysine (1 hour, 10 mkM) with subsequent drug removal caused the irreversible damage of DNA reparative processes at the stage of short fragments' suturing.

[Localization of metronidazole in the organs of tumor-bearing animals using electron paramagnetic resonance]. / Izuchenie lokalizatsii metronidazola v organakh zhivotnykh-opukholenositelei metodom élektronnogo paramagnitnogo rezonansa.

The low-temperature ESR-spectroscopy was used to study the irradiated organs and blood of tumor-bearing animals before and after the administration of metronidazole. The ESR signals of metronidazole anion-radicals were registered in tissues of the animals injected with metronidazole: the intensity of these signals correspondent with the tissues preparation content.

[Selective shedding of gangliosides by cells of mouse ascitic sarcoma-37]. / Izbiratel'noe sbrasyvanie gangliozidov kletkami astsitnoi sarkoma-37 myshei.

The profile and content of gangliosides associated with tumour cells of mouse sarcoma-37 and exfoliated from the cell surface were determined. It was shown that 20% of tumour gangliosides shed from the cell surface and only about 7% of all the shed gangliosides were contained in plasma membrane fragments. When incubated in vitro at 37 degrees C for 1 hour, the tumour cells were found to release less than 2% of cellular gangliosides. The main components of cellular gangliosides corresponded in their chromatographic behaviour to GM2 (31-32% of the total ganglioside content), GD3 (17-18%), GD1a (9-11%), GD2 (16-17%) and hematosides (19-21%). The profiles of in vivo and in vitro shed gangliosides were similar but strongly differed from those of cellular gangliosides: the relative content of GM2 was 70-75% and the other gangliosides were found in negligible amounts. The data show that GM2 accumulation in extracellular spaces is rather the result of its selective shedding than the shedding of products of "incomplete" cellular ganglioside synthesis.