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Biomedical subjects

A S Saenko

Publications and source records attributed to A S Saenko.

At least 37 records · Page 2Linked to original sources

[Mechanism of the cytotoxic action of formaldehyde on cultured mammalian cells].

Induction and repair of DNA lesions cell inactivation and repair of potentially lethal damages (PLD) were studied after the treatment of cultured cells with formaldehyde. Formaldehyde induced the appearance of a rapidly sedimentating DNA--membrane complex. This complex may contain up to 50% of choline and no more than 3-5% of leucine or lysine incorporated in the acid insoluble cell fraction, Inhibition of DNA synthesis, induction of single strand DNA breaks and/or alkali-labile sites increased with the raise of formaldehyde concentration. A good correlation is observed between with the raise of formaldehyde concentration. A good correlation is observed between with the raise of formaldehyde concentration. A good correlation is observed between the increasing DNA quantities in the rapid sedimentation complex and the cell lethality.

Animals↗

[Characteristics of DNA synthesis in Chinese hamster cells in exponential and stationary culture growth stages after cell exposure to elevated temperature].

Hyperthermia (43 degrees C for 1 hour) is shown to induce a reduction of DNA synthesis and a change in molecular weight distributions in the pool of newly synthesized DNA in cultured Chinese hamster cells. The DNA synthesis inhibition extent as well as the character of disturbances in DNA replication are different in cells of the exponential and the stationary cultures.

Animals↗

Proliferative activity and radiosensitivity of human tumors.

On surgery material and biopsies from human tumors of various types investigation of labeling index and growth fraction in vitro, cell survival and cell population kinetics in diffusion chambers and changes in the cell kinetic parameters after irradiation were performed. The analysis of results obtained using the diffusion chambers and in vitro system demonstrate variability in labeling index within tumors of various type, individual differences and variation within the same tumor. Significant variability of growth fraction in individual tumors was also noted, however, in many instances, the most of cells in tumor were not proliferating. The growth fraction in gliomas and tumors of the floor of mouth was greater in tumors with high labeling index, in patients with a short tumor history and in patients with the short nonrelapse period. In the same groups of tumors changes of labeling index growth fraction during radiotherapy were compared with the therapeutic response of tumors. It can be concluded that the initial parameters of proliferative activity (labeling index and growth fraction) did not determine the radiation response of tumors but the dynamics and the intensity of their changes during the treatment were more informative in this respect. Complete regression of tumor may be expected only with decrease of labeling index and growth fraction.

Cell Division↗

[Effect of carminomycin on the structural integrity, primary susceptibility to radiation damage and the postradiation repair of the cellular DNA-membrane complex in Ehrlich's ascitic carcinoma].

It was found with the method of sedimentation analysis in sucrose alkaline gradients that carminomycin induced in vivo degradation of the DNA-membrane complex of the Ehrlich's ascites carcinoma cells (EAC). The concentration dependence of the complex damage correlated well with the data on the cell survival: the subtoxic concentration of the antibiotic according to these tests was 0.001 micrograms/ml. Combined effect of carminomycin in the subtoxic concentration and gamma-radiation on the cells did not result in any increase in the primary radiation damage to the DNA-membrane complex. Still, it inhibited its post-radiation reparation. This suggested that on the combined use of the above damaging agents the antibiotic significantly increased the effect of the ionizing radiation on the cells.

Animals↗

[Action of carminomycin on the structural integrity, primary damage susceptibility and postradiation regeneration of the DNA from Erhlich's ascitic carcinoma].

Carminomycin added to the cell culture of Ehrlichs ascites carcinoma (EAC) induced single breaks in DNA whose number increased proportionally to the amount of the antibiotic and the incubation time with it (up to 1 hour). The relationship between the incubation time and DNA injury is first of all defined by the necessity for the antibiotic metabolic activation or the properties of endonucleases. No increase in the number of one-thread breaks during the incubation period of 60 to 120 minutes indicated a possible reparation of DNA injury induced by the antibiotic in the late periods. The exposure of the EAC cells to carminomycin before gamma-irradiation did not result in any increase in the primary radiation injury to DNA but suppressed DNA postradiation reparation.

Animals↗

[Role of carbamoylation processes in the cytotoxic action of nitrosoalkylureas].

The treatment of an asynchronous LL cell line population, being in the log phase of growth, with isocyanate (one of the nitrosourea degradation products) results in the cell death of about 50% of the whole population. The other part of this cell population is unsensitive to this chemical, even at concentrations 100 times more than those equal the LD50 doses. The cell death is due neither to inhibition of DNA-synthesis nor to DNA (single or double strand) breaks or DNA-membrane complex degradation. It is assumed that a mechanism highly sensitive to carbomoylation may be operating in some period of the cell cycle.

Alkylation↗

[A method for determination of alkaline sucrose gradient sedimentation patterns of DNA for nondividing and slowly dividing cells].

A radiometric method for developing the alkaline sucrose gradient sedimentation patterns of DNA from non-labeled cells is described. The method is based on labeling of DNA in the gradient fractions by means of a labeled amino acid binding to DNA in the presence of formaldehyde. The procedure involves incubation of the fractions with a mixture of the labeled amino acid and formaldehyde, filtration of the incubation mixtures through nitrocellulose filters and radiometry of the filters. Relationship between the radioactivity on the filter and DNA concentration in the sample is linear. DNA detection sensitivity and specificity are satisfactory for the use under gradient ultracentrifugation condition. The non-labeled cells DNA sedimentation patterns developed by the method described and those of DNA from the same cells labeled with 3H-thimidine in vivo are found to be similar.

Amino Acids↗

The role of DNA polymerase I in genetic recombination and viability of Escherichia coli.

The rate of formation of high-molecular-weight daughter DNA in the conditionally lethal double mutant polA12 uvrE502, incubated at nonpermissive temperature, was slower than that in the single polA12 mutant. There exist at least two pathways determining viability of Escherichia coli cells: one of them is dependent on polA+ and recB+ genes, while another is polA+ and recB+ genes, while another is polA recB independent but requires the uvrE+ gene and can be blocked by exonuclease I. The RecF but not the RecBC pathway of genetic recombination was found to be absolutely dependent on the polymerizing activity of DNA polymerase I. The involvement of DNA polymerase I in genetic recombination in the recB- C- sbsB strain and viability in the uvrE- or recB- strains suggest the existence of the common steps required for the accomplishing of the RecF pathway of recombination and for viability of E. coli.

Cell Survival↗

Genetic analysis of a temperature-resistant revertant of the conditional lethal Escherichia coli double mutant polA12 uvrE502.

Conditional lethality of the Escherichia coli polA12 uvrE502 double mutant may be overcome by a mutation that has been termed polA350. The polA350 mutation restored the polymerizing activity of deoxyribonucleic acid polymerase I at 42 C in the polA12 mutant and partially suppressed ultraviolet (UV) and methylmethane sulfonate sensitivities of the polA12. Mapping experiments have located polA350 between metE and polA12, very close to the latter. The strain carrying polA12 polA350 and recB21 was viable at 42 C. The effects of the recB21 and polA12 polA350 combination on the UV sensitivity were additive. The triple mutant polA12 polA350 uvrE502 was more UV sensitive than the single uvrE502 mutant.

Alkanesulfonates↗

[Results of and prospects for methods of determination of the frequency of mutant cells for glycophorin A and T-cell receptor loci to estimate long-term genotoxic effect of ionizing radiation].

The usage of two methods for assessment of somatic gene mutations for the purpose of biological dosimetry and estimation of consequences of irradiation at long time after the exposure has been discussed. The determination of cells bearing mutated glycophorin A (GPA) locus is a reliable method for biodosimetry at both short and long time after the acute irradiation according to our results and the data of other authors. For prolonged exposure, the GPA-method is less informative than in cases of acute irradiation. The determination of mutant cell frequency at T-cell receptor (TCR) locus may be used only at short time after the irradiation. Meanwhile, the TCR-method is more sensitive and informative for biodosimetry of recent irradiation than the GPA test. The both methods may be used for individual assessment of long-term health consequences after the irradiation, because persons with elevated frequencies of mutant cells may represent a group at high risk in respect to oncological diseases.

Gene Frequency↗