[Changes in the replication apparatus and phosphorus-containing metabolite pool in experimental tumors in animals during development]. / Izmeneniia v apparate replikatsii i sostoianii pula fosforsoderzhashchikh metabolitov éksperimental'nykh opukholei zhivotnykh v protsesse razvitiia.

Activity of replicase complex enzymes involving thymidine kinase (TK), ribonucleotide reductase (RR), DNA-polymerases alpha and beta as well as DNA synthesis and single breaks in DNA were studied during growth of P388 ascites tumor. Under these conditions the rate of DNA synthesis was distinctly decreased via salvage pathway and de novo. Single breaks were not detected in the preexistent DNA within various periods after transplantation of P338 leukemic cells. Retardation of DNA synthesis during tumor growth correlated with a decrease in TK, RR and DNA-polymerase alpha activities, while DNA-polymerase beta activity was markedly increased. Growth of melanoma B16 was accompanied by a decrease in content of ATP, ADP, NAD, phosphocreatine and phosphosaccharides as well as by an increase in the level of inorganic phosphates.

[Biochemical mechanisms of resistance to a new antineoplastic drug CRC 680578 from the nitrosourea class]. / Biokhimicheskie mekhanizmy rezistentnosti k novomu protivoopukholevomu preparatu iz klassa nitrozomochevin CRC 680578.

The biochemical mechanisms of resistance to CRC 680578, a new antitumour chloroethylnitrosourea alpha-amino acid derivative, were studied. Alterations in DNA, RNA and protein syntheses, SH-group content, drug efflux, activities of replicative and repair enzymes, such as ribonucleotide reductase, thymidine kinase, O6-alkylguanine-DNA-alkyltransferase and DNA polymerases alpha and beta and damages of the DNA secondary structure were investigated in sensitive and resistant to CRC 680578 leukemia L1210 cells. It was found that the total SH-group number in drug-resistant cells was increased (about 1.3-fold in comparison with sensitive cells) which seems to be due to the mechanisms of drug resistance. CHC 680578 induced less pronounced inhibition and more rapid restoration of DNA and RNA synthesis in resistant cells. No differences between the ribonucleotide reductase and thymidine kinase activities were found either in intact cells of the both strains or after drug administration. The efficiency of repair of DNA chloroethyl adducts by O6-alkylguanine-DNA-alkyltransferase in leukemia cells of various sensitivity was found to be identical. The differences in enzyme activities in intact cells of the both strains were insignificant. It was supposed that factors other than changes in the level of O6-alkylguanine-DNA-alkyltransferase in leukemia cells may be responsible for the resistance to CRC 680578. The increase in the levels of DNA polymerase alpha and, especially, of DNA polymerase beta, in sensitive (but not resistant) mouse leukemia cells 48 hours after drug administration is though to define the mechanism of resistance to the new antitumour agent CHC 680578.

[The EPR spectra of the ribonucleotide reductase in the tumorous tissues and organs of tumor-bearing animals]. / Spektry EPR ribonukleotidreduktazy v opukholevykh tkaniakh i organakh zhivotnykh-opukholenositelei.

Ribonucleotide reductase activity (RRA) has been studied in various tumors and spleens of tumor-bearing animals using EPR technique and biochemical methods. The effect of a number of biologically active compounds on RRA has also been studied. RRA in tumor and spleen increases during tumor growth. Inhibitory effect of irradiation, hydroxyurea, nitrosomethylurea and activatory effect of 5-nitrofurans and nitroimidazole derivatives on RRA has been observed. Regulatory factors of RRA and DNA synthesis in vivo have been discussed.

[Modification by cystamine of radiation-induced free radical damage to biomolecules in tissues of mouse organs]. / Modifikatsiia tsistaminom radiatsionnykh svobodnoradikal'nykh povrezhdenii biomolekul v tkaniiakh organov myshei.

The method of low-temperature ESR-spectroscopy was used to study a modifying effect of cystamine on the yield of radiation-induced free radicals in different biomolecules of liver and spleen tissues of mice. Intraperitoneal administration of cystamine (150 mg/kg) 15 min before isolation and freezing of the tissues was shown to reduce by 11 per cent the yield of radicals of H-adducts of thymine DNA bases, to decrease by 23 per cent the yield of radicals of triacyglycerol and phospholipid radiolysis, and to increase by 24 per cent the yield of radicals of lipid fatty acid residues in splenic tissue. According to the criterion used, cystamine has no modifying action on the yield of free-radical damages to liver biomolecules.