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Biomedical subjects

I S Sokolova

Publications and source records attributed to I S Sokolova.

At least 19 recordsLinked to original sources
PubMed1999

[The new antitumor drug cycloplatam: cytotoxicity and DNA interstrand cross-linking].

Cytotoxicity genetic mechanisms such as induction of SOS-repair, excision repair and interstrand coupling induced by cycloplatam or ammine (cyclopentyl amine)-S(-) malatoplatinum (II), a new antitumor drug, were for the first time studied in comparison to those of the known drug cis-diammine dichloroplatinum (II) (DDP) in a model system of Escherichia coli. In the cells of E. coli the cycloplatam cytotoxicity was much lower than that of DDP. Both the drugs induced SOS-repair in E. coli PQ37. In a concentration of 25 microM DDP was 20 times as active as cycloplatam. In concentrations of 40 to 100 microM the difference leveled. Both the drugs induced interstrand coupling in specimens of pure DNA from calf thymus and E. coli. When the cells of the wild type E. coli AB1157 were incubated in the presence of the drugs only DDP induced the DNA interstrand coupling. No correlation between the DNA interstrand coupling induced by cycloplatam or DDP and cytotoxicity of the drugs was observed.

Animals↗
PubMed1995

[Modulation of the antitumor activity of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosoure a by O(6)-methyl-2'-deoxyguanosine--a new inhibitor of O(6)-alkylguanine-DNA-alkyltransferase].

O6-Methyl-2'-deoxyguanosine (O6-MedG), a novel inhibitor of O6-alkylguanine-DNA alkyltransferase (O6-AGT), has been synthesized. The ability of O6-MedG to deplete the O6-AGT activity in leukemia L1210 and melanoma B16 cells in vivo has been studied. After intraperitoneal administration of O6-MedG to mice bearing leukemia L1210 or melanoma B16, the activity of O6-AGT in tumour cells decreased by 50%. Pretreatment of leukemia L1210 bearing mice with O6-MedG (200 mg/kg) 24 hours prior to ACNU (15 mg/kg) administration resulted in six out of seven 60-day survivors. Treatment of mice with ACNU (15 mg/kg) alone increased the life span by 200%. Treatment of melanoma B16 bearing mice with O6-MedG and 3 hours thereafter with ACNU resulted in a 50% inhibition of tumour growth, whereas the inhibiting effect of ACNU alone was 16%. There was no difference in leukemia growth when L1210/BCNU bearing mice were treated with O6-MedG followed by ACNU treatment. In vivo ACNU (15 mg/kg) produced a deep and prolonged inhibition of DNA, RNA and protein synthesis in leukemia L1210 cells. The DNA synthesis in leukemia L1210/BCNU cells was shown to recover more rapidly than in L1210 cells. The activities of DNA-polymerases alpha and beta and, especially, of O6-AGT were elevated in ACNU-resistant leukemia cells as compared with ACNU-sensitive cells. The activation of some repairing enzymes, such as O6-AGT, DNA-polymerases alpha and beta as well as increased levels of GSH may play a role in the development of drug resistance to ACNU.

Animals↗
PubMed1992

[Formation of superoxide radicals in membranes of subcellular organelles in regenerating liver].

A correlation between the changes in the rates of superoxide radical generation, upsilon, in microsomes, mitochondria, and nuclei and the Cu, Zn- and Mn-SOD activities in rat liver during the first 5 days after partial hepatectomy, has been studied. Level of upsilon in microsomal and mitochondrial membranes in the regeneration process was reduced. The Cu, Zn- and Mn-SOD activities changed in an extreme and antibate manner: the former was characterized by a minimum, whereas the latter-by a maximum with an extreme on the 3rd day after surgery. Analysis of the correlation between the values of upsilon in the nuclear membranes and cell cycle stages (on a literary basis) revealed that the upsilon was decreased 2 times on the stage of DNA synthesis. When mitosis was at maximum, upsilon showed a 4-5-fold increase in comparison with the control, the Cu, Zn-SOD activity being essentially unchanged. A role of SOD and O2-. in cell division is postulated. O2-. is assumed to play a role in gene expression, disassembly, and regeneration of the nuclear membrane; that of SOD is thought to consist in regulation of the proliferative activity.

Animals↗
PubMed1990

[14Co-dimetinur distribution in mice in relation to the stage of the development of tumor process].

Pharmacokinetics of the antitumour agent 14CO-dimetinur (100 mg/kg) after oral administration to the intact mice and those with solid leukemia P 388 is characterized by its rapid delivery to organs and tumours with the achievement of maximum radioactivity 5 hours later and the further gradually decline during 4 days. The increased accumulation of the 14CO-products in kidneys and their retarded output from the brain and lungs against a background of the relatively equal distribution of radioactivity between other tested organs have been established. The same level of carbamoylated products in large tumours (the 16th day after leukemia transplantation) as well as in small tumours (the 9th day after inoculation) is in agreement with the conservation of the initial marked inhibitory effect of the drug against advanced tumours.

Administration, Oral↗
PubMed1990

[The mechanisms of a decrease in the toxic action of cisplatin when administered jointly with preparation K-2-9 to mice with melanoma B16].

The K-2-9 preparation was determined to change cis-platinum pharmacokinetics, that resulted in its pharmacodynamics alterations. The higher Pt concentrations in the blood of animals which were given the K-2-9 preparation provided selectivity of cytostatic accumulation in the tumour tissue, that was accompanied by more prolonged inhibition of the DNA synthesis. A decrease in the toxicity of cis-platinum is associated with a change in the elimination pathway and acceleration of its removal from the organism.

Animals↗
PubMed1987

[Contrast and quantitative characteristics of biological tissues in experimental neoplastic processes based on biexponential relaxation analysis of NMR tomograms].

A method of contrast enhancement and quantification of experimental tumors in vivo by estimation of tissue proton transverse magnetic relaxation nonexponentiality is proposed. Relaxation time and percentage of a rapidly descending magnetization component due to intracellular water protons are followed for tumor and uninvolved tissues in a course of subcutaneously transplanted solid mouse melanoma B16 development. The exponential approximation of a relaxation curve within the 6-90 ms time range is shown to fit melanoma B16 tissue characterization. Contrast-enhanced calculated MR-images are presented.

Animals↗
PubMed1984

[Effect of 1,2:5,6-dianhydrogalactitol and 1,2:5,6-dianhydro-3,4-diacetylgalactitol on DNA synthesis in the cells of melanoma B16, bone marrow, small intestine epithelium, spleen and liver of mice].

Alterations in DNA synthesis induced by 1,2:5,6-dianhydrogalactitol (DAG) and 1,2:5,6-dianhydro-3,4-diacetyldianhydrocalactitol (Diac-DAG) were studied in host normal cells and tumor cells. After administration of these antitumor drugs to melanoma B16-bearing mice, DNA synthesis in host tissues (bone marrow, gastrointestinal mucosa, spleen, liver) got recovered more rapidly than DNA synthesis in melanoma B16. Diac-DAG differed from DAG from the standpoint of damage to DNA synthesis in normal cells. Only DAG inhibited the DNA synthesis in liver cells. Inhibition of DNA synthesis in the bone marrow and spleen with Diac-DAG was less remarkable than with DAG.

Animals↗
PubMed1984

Damages of DNA synthesis in normal and tumor cells with sugar alcohol derivatives.

The rates of incorporation of 2-14C-thymidine into DNA of melanoma B16, bone marrow, gastrointestinal mucosa, spleen and liver at various time after administration of dianhydrogalactitol (DAG), 3,4-diacetyldianhydrogalactitol (DiacDAG) and 3,4-disuccinyldianhydrogalactitol (DisuDAG) at maxima nonlethal single doses to tumor-bearing mice were studied. The sugar alcohol derivatives induced the stable inhibition in DNA synthesis of tumor cells. DNA synthesis in normal dividing cells was shown to recover more rapidly than in melanoma B16 cells after administration of all drugs. DisuDAG is characterized by stronger inhibitory effect on DNA synthesis in melanoma B16 cells at the half of the single maxima nonlethal dose compared with DAG and DiacDAG. Differing from DAG, DiacDAG and DisuDAG did not effect the incorporation of 2-14C-thymidine into DNA of liver cells. In vivo inhibition of DNA synthesis in melanoma B16 cells with DiacDAG was not due to damage of the TCA soluble fraction.

Animals↗
PubMed1979

[Kinetics of macromolecular carbamoylation in normal and tumor cells after the administration of N-methyl-N-nitrosourea-14CO].

The pharmacokinetics of N-methyl-N-nitrosourea-14CO (14CO-MNU) was investigated in hepatoma 22a tumor-bearing and normal mice at various time after a single intravenous injection (80 mg/kg). The rapid clearance of 14CO-MNU from plasma of the mice was observed 5 hours following the administration of the drug. Peak levels of radioactivity in the hepatoma were noted 48 hours after the administration of 14CO-MNU, while the liver, kidney, spleen and intestinal epithelium showed an insignificant radioactivity at this time both in normal and tumor-bearing mice. The analysis of the radioactivity distribution among macromolecules (DNA, RNA, protein) and lipids indicated the highest label in lipids of all organs.

Animals↗
PubMed1977

[Kinetic study of the effect of N-nitroso-N-alkylurea on the development of leukemia L1210].

A comparative kinetic study of antitumor activity of seven alkyl derivatives of nitrosourea in the process of ascites leucosis L 1210 was undertaken. The efficacy was estimated on the basis of determining the coefficient of inhibition chi and the increase of an average survival of treated mice. The tumor was found to be mostly sensitive to nitroso derivatives containing chloroethyl groups--1,3-bis (2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-(3-cyclohexil)-1-nitrosourea, 1-(2-chloroethyl)-3-(4-methylcyclohexil)-1-nitrosourea. 1-nitroso-1-methylbiuret and 1-nitroso-1-methylurea proved to be highly effective too, while 1,3-dimethyl-1-nitrosourea and 1,3-diethyl-1-nitrosourea were found to be insignificantly effective.

Animals↗
PubMed1976

[Effect of N-nitroso-N-methylurea on DNA and RNA synthesis in cells of liver and spleen tumors in leucosis L-1210].

During the development of leucosis a progressively retarded incorporation of 2-C14-thymidine and C14-uridine into DNA and RNA of a separate tumor cell and an active incorporation of 2-C14-thymidine into DNA of hepatic and splenic cells were observed. Repeated injections of NMU (20 mg/Kg X 5) in tumor-bearing animals result in a twice increase of life terms in mice and suppression of total tumor cells growth. The observed therapeutic effect is related with deep inhibition of DNA and RNA synthesis in leucosis L-1210 cells, while DNA synthesis in hepatic and splenic cells is only insignificantly suppressed (compared with the normal level typical for intact animals), but RNA synthesis in these organs is actually not involved.

Animals↗