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Biomedical subjects

A N Chebotarev

Publications and source records attributed to A N Chebotarev.

At least 19 recordsLinked to original sources

Enhanced expression of 1p32 and 1p22 fragile sites in lymphocytes in cutaneous malignant melanomas.

Frequency and distribution of 5-fluorodeoxyuridine (5-FdU) plus caffeine-induced fragile sites on chromosomes of peripheral blood lymphocytes (PBL) from 10 patients with cutaneous melanoma were studied in comparison with 10 PBL samples from normal donors of corresponding sex and age. The total number of breaks showed a significant difference among individuals in both groups, however, the average frequencies of 5-FdU plus caffeine-induced, as well as spontaneous damages in PBL from melanoma patients, were higher than those from healthy volunteers. The analysis of the breakpoint distribution showed a statistically significant increase in the expression of several fragile sites. The highest enhancement was observed at 1p32 and 1p22 sites (p less than 0.001). Earlier, the increase in the expression of 1p32 fragile sites was reported for neuroblastoma patients. We believe that enhanced expression of fragile sites in 1p may play a yet-unknown pathogenetic role in the development of some neuroectodermal tumors.

Adult

[Mathematical modeling of the dynamics of frequency of the mutation process. I. Age features of SA frequency dynamics tendency].

A mathematical method for modelling SA frequency dynamics tendencies, depending on age, for different fixation moments and in general for the whole interval of observation is suggested. The criteria of remainder dispersion attitude is used for choosing an optimal model. The initial hypothesis about discrepancies distribution law is used for checking adequateness of the optimal model to the research process. In addition, aposteriory trust intervals are built for the initial and forecast SA frequency values and the hit into them corresponding the experimental values of SA frequencies is controlled. An example of practical realization of the model proposed is considered and the results obtained analysed.

Models, Theoretical

[Decrease of incidence of chromosome aberrations after a course of hyperbaric oxygenation].

The influence of the course of hyperbaric oxygenation (HBO) on the peripheral blood lymphocytes chromosomes of 7 patients with different pathology and of 3 healthy volunteers was studied. It is proved that after HBO course the frequency of chromosome, aberrations of chromatid type hasn't been practically changed whereas the frequency of aberrations of chromosome type significantly decreases by three times on the whole.

Cells, Cultured

[Revision of th distribution of chromosome aberrations induced by chemical mutagens using the BUDR label].

Cell distribution was analysed with the help of the BrDU label for the number of chromosome aberrations and breaks induced by one-center (thiophosphamide and phosphamide) and two-center (dipine and fotrine) mutagens at the stage G0 in the Ist mitosis of human lymphocytes harvested at different times of culturing (from 56 to 96 h). The comparison was made between the type of aberration distribution in cells and the dependence of their frequency on the harvesting point for various mutagens. Poisson aberration distribution in cells for two-center mutagens was found to correspond to their constant frequency observed at different times of harvesting. On the other hand, for one-center mutagens, a geometrical distribution of chromosome breaks corresponded to an exponential decrease in their frequency in time. It is suggested that two-center chemical mutagens and ionizing radiation cause largely short-live damages which are realized into chromosome aberrations rather quickly (during one cell cycle). One-center mutagens, however, cause such damages that the probability of their transformation into chromosome aberrations is decreasing rather slowly in time, under the exponential law, and their realization into chromosome aberrations can occur in subsequent cell cycle.

Bromodeoxyuridine

[Interchangeability of mutagens during fractionated effects of unequal concentrations of alkylating agents].

The ability of thiophosphamide and dipin to substitute for each other in "clastogenic adaptation" of human lymphocytes was investigated at Go phase. There were used 5 low concentrations of mutagens 2, 0.2, 2.10(-2), 2.10(-3), 2.10(-4) micrograms/ml and the high one of 20 micrograms/ml with which cells were treated 2 hr after the effect of low concentrations. The "protective" concentrations for both mutagens were 0.2, 2.10(-2), 2.10(-3) micrograms/ml. The pretreatment with thiophosphamide caused the decrease in chromatid aberrations in "challenge" treatment with dipin, the pretreatment with dipin caused the decrease in chromosome aberrations in "challenge" treatment with thiophosphamide.

Alkylating Agents

[Effects of exposure time using preliminary concentrations on the mutagenic effect of the basic action of one-center and dual-center mutagens].

The effect of exposition with pretreatment for thiophosphamide and dipin of human lymphocytes at Go phase was investigated. There were used 5 low concentrations of mutagens: 2, 0, 2; 2.10(-2); 2.10(-3), 2.10(-4) mcg/ml with different exposure: 1/4 hr, 1/2 hr, 1 hr and 4 hr and high concentration of 20 mcg/ml by which cell have been treated. There was discovered the dependence of the "protective" concentration on the exposition: the increase of exposition of pretreatment induced the decrease of "protective" concentration and vice versa.

Alkylating Agents

[Frequency of chromosome aberrations induced by mutagens of various functions in cells of the first division at various times of fixation].

The dynamics of chromosome aberrations in human lymphocyte culture cells of the 1-st division after exposure in the G0 phase for 1h to functionally different alkylating mutagens - ethyleneimine derivatives (bifunctional phosphamide, threefunctional thiophosphamide, tetrafunctional dipine and pentafunctional photrin) was analysed. The frequency of chromosome aberrations was constant after exposure to "dicentric" mutagens (dipine, photrin) at all times of fixation, while under the action of "monocentric" mutagens (phosphamide, thiophosphamide) this declined significantly with increasing the duration of cultivation. The portion of aberrations of the chromatid remains unaltered in time, in case of both "dicentric" and "monocentric" mutagens, reaching 75% for "monocentric" and 50% for "dicentric" of the total number of chromosome aberrations.

Chromosome Aberrations

[Simultaneous estimation of sister chromatid exchange and evaluation of cell cycle delay].

The frequency of sister chromatid exchange and cell cycle duration were evaluated simultaneously. This approach is based on the analysis of distribution of cells with differential staining of sister chromatids after treatment of cells with 5-bromodeoxyuridine. The treatment of cells with thiotepa caused no changes in cell cycle duration, while the combination of thiotepa and hydroxyurea (HU) or cytosine-beta-D-arabinofuranoside (ARA-C) was observed to prolong cell cycle duration. Furthermore, it has been shown that caffeine, HU, ARA-C do not increase frequency of sister chromatid exchange in control cells and in cell treated with thiotepa.

Animals

[Thiophosphamide induction of sister chromatid exchanges at various phases in the cell cycle of a Chinese hamster cell culture].

Influence of three concentrations of thiophosphamide (thioTEPA) on the formation of sister chromatid exchanges (SCE) has been studied at different phases during 2 cell cycles in cultured Chinese hamster cells. It is shown that the frequency of SCE does not differ from the control level under the effect of the mutagen on cells in the G2 phase of the first cell cycle from the moment of harvesting. Thiophosphamide induces the same number of SCE at S, G1 stages of the first cell cycle and G2 of the second one till the moment of harvesting. The number of SCE correlates in a direct proportion with a concentration of thiophosphamide. A scheme of forming SCE is proposed.

Animals

[Quantitative analysis of sister chromatid exchanges in the cell].

Assuming a random nature of distribution of sister chromatid exchanges (SCE) in a karyotype, the formulae have been obtained allowing the calculation of the number of SCE that are overlooked because of a limited resolving power of the SCE detection method. The results obtained mean that the actual number of SCE is more than the observed one, the part of overlooked exchanges being increased with the heightening of the SCE level. Taking into account overlook exchanges, the formula has been obtained that makes possible the calculation of the expected number of SCE observed in any group of chromosomes. These results were applied in the analysis of the SCE distribution among chromosomes. A better conformity has been obtained between the expected results and the observed ones, than under the assumption that the observed SCE are distributed in proportion to the lengths of chromosomes. The obtained formulae are of use in interpreting the lack of the observed SCE in small chromosomes and the excess of them in large ones.

Animals

[Modified method of differential staining of sister chromatids].

A modified method of obtaining differential staining of sister chromatids is described. It is simple, rapid, and effective, and at the same time inexpensive and accessible, since it allows one to use available reagents. When 5-bromdeoxyuridine was administered 24 hours before fixation into the Chinese hamster cell culture the percentage of metaphases with a differential chromatid staining constituted 95--98, and when this substance was administered 28 hours before fixation into the human lymphocyte culture this percentage varied from 75 to 92, depending on the individual. The mean number of sister chromatid exchanges in human lymphocytes failed to depend on the time of fixation.

Animals

[Cytogenetic effect of cyclophosphamide in a culture of human lymphocytes following its activation in the bodies of mice].

Cytogenetic effect of cyclophosphamide in cultured human lymphocytes after its activation in C57BL/6 mice in vivo was investigated. Cyclophosphamide was injected intraperitoneally in mice for 30 min. at doses of 200, 400, 600, 800 and 1000 mg/kg. Blood serum with activated metabolites of cyclophosphamide was added to human lymphocyte culture. The dependence of the part of aberrant metaphases on the concentration of cyclophosphamide after the activation can be presented as equation rho==1-e-(KC+alpha)2 and the total number of breaks as X=e(KC+alpha)2-1, where rho is a part of aberrant metaphases, X is a number of breaks of chromosomes per cell, C is the concentration, K and alpha are coefficients. The part of chromatid breaks from the total number of chromosome damages is constant for all concentrations and the comprises on the average 79,11%. Only the chromatid type of exchanges are observed. Distribution of chromosome breaks in cells corresponds to geometrical, but not to Poisson's distribution. Cyclophosphamide belongs to the group of one-sited mutagens in its cytogenetic chatacteristics. The alkylating activity of cyclophosphamide metabolites, estimated by means of NBP test, increases up to the dose 400 mg/kg and then remains constant for the strain of mice studied, cytogenetic activity increasing. Cyclophosphamide does not produce cytogenetic activity without activation. To test chemical substances for mutagenic activity, it is suggested to activate them in the mouse organism with the following administrating blood serum of these animals with the metabolites of tested (or with primary) substances in the study of their mutagenic activity on human lymphocyte culture.

Animals

[Dependence of the cytogenetic effect on TEPA concentration in human lymphocyte culture].

The authors studied the cytogenetic action of TEPA (tris/2-methyl-1-azyridinyl) on the human lymphocyte culture. It was shown that the increase of the mutagen concentration from 0.125 to 16.0 microgram/ml the cytogenetic effect for the portion of the aberrant metaphases rose from 6.0 to 61.0%, and for the total number of ruptures - from 7.96 to 116.3. A method of finding the least effective concentration of the substance under study in comparison with control is suggested; for TEPA it constitutes 0.120 microgram/ml. The percentage of chromatide ruptures remained constant in using different TEPA concentration and constitutes 51.72%. Cell distribution of chromosome ruptures is satisfactorily described by geometrical distribution.

Azirines

[Study of the decomposition of alkylating mutagens of the ethyleneimine series in human lymphocyte cultures].

A simple method of determination (with a high reproducibility) of concentrations of the alkylating compound in the culture medium is described. Thiophosphamide failed to decompose in the course of 24 hours either in the culture mixture or in the human lymphocyte culture. As to phosphamide, dipine and fotrin, these drugs disintegrated significantly in the culture during 24 hours, but not in the course of the first 6 hours.

Alkylating Agents

[Relationship between the cytogenetic effect of different concentrations of thiophosphamide and phosphemide and the duration of their contact with human lymphocytes].

The effect of thiophosphamide at conccentrations of 10, 20 and 30 mcg/ml and phosphamide at concentrations of 35 and 50 mck/ml on human lymphocyte chromosomes at different time of the contact was investigated. The experiments were carried out at GO phase (before adding FGA) at 37 degrees C from 10 to 240 minutes. The fixation was made within 58th hour. A mathematical model, satisfactory describing experimental data on the reaction of mutagen-chromosome interaction during the time of exposition, is suggested. According to this model, the following equation are obtained: rho = (1 - e-(alpha+Kt))2; chi = (see article), where rho is a portion of aberrant cells, chi is the average number of breaks per cell, t is the time of exposition of mutagens with cells, alpha and K are coefficients. Breaks induced by thiophosphamide and phosphamide are distributed among cells according to geometrical parameter under any experimental conditions. The portion of chromatid breaks did not change at any exposition time for both mutagens and remained on the level of 76,53%. The proportion of symmetric and asymmetric exchanges under different experimental conditions did not differe from 1 : 1. The prabability of the formation of complete exchanges in the case of the action of thiophosphamide was higher than in the case of phesphamide.

Cells, Cultured