Search PubMed⌕ Search

Biomedical subjects

A N Chebotarev

Publications and source records attributed to A N Chebotarev.

At least 55 records · Page 3Linked to original sources
PubMed1983

[Proliferative activity of lymphocyte cultures due to the mutagenic action of thiophosphamide in vivo and in vitro].

Thiophosphamide is capable of inhibiting the cell cycle after the treatment of rabbit blood lymphocytes in vivo and in vitro. To assess the proliferative activity of the cells during cultivation, use was made of the index of the mean division number which was experienced by the cells after mutagenic exposure prior to fixation. As the mutagen dose was raised in vivo and in vitro, the mean division number decreased linearly, namely by approximately the same value with an equivalent dose variation. This indicates that thiophosphamide produces the same cytotoxic action both in vivo and in vitro.

Animals↗
PubMed1982

[Comparison of the frequency of chromosome aberrations induced by thiophosphamide in rabbit lymphocytes in vitro and in vivo].

Rabbit lymphocytes were treated with thiophosphamide in vivo and in vitro. In-vitro doses were calculated by multiplying thiophosphamide concentrations by the time of treatment (the doses ranged within 0-1500 mg/min/ml). In-vivo doses were calculated as integral of thiophosphamide concentration function from the time of administration till the time of blood sample collection (the doses ranged within 0-1900 mg/min/ml). It was shown that with the dose increase the rate of chromosome aberrations and the number of disruptions per cell rise exponentially in vivo and in vitro. At the same time the parameters of regression equations coincide. This evidences that thiophosphamide produces the same effect in vivo and in vitro.

Animals↗
PubMed1982

[Analysis of sister chromatid exchanges in the 1st, 2d and 3d mitoses using 5-bromodeoxyuridine and 5-bromodeoxycytidine].

The cultures of Chinese hamster cells were treated with different concentrations (2.5, 5.0, 10.0, 20.0, 80.0 and 160.0 microgram/ml) 5-BrdU and 5-BrdC during 12 hours. The cultures were fixed at the 24-th hour. The linear increase of sister chromatid exchanges (SCE) was discovered with the increase of BrdU concentration. No change of SCE frequency was observed at different BrdC concentrations. The reasons for these differences in a concentration effect are discussed.

Animals↗
PubMed1982

[Relation of the effectiveness of inducing sister chromatid exchanges to the chemical structure of the mutagen].

The activity of 12 alkylating compounds of different chemical structure has been investigated for the induction of sister chromatid exchanges (SCE) in a cell culture of Chinese hamster. A linear dependence of SCE upon the concentration has been found for all alkylating compounds. The activity for SCE induction depends upon the chemical structure of the mutagen: benzochinone derivatives (trenimon, E39) and triazine (TEM) are more effective than the derivatives of amidophosphoric acid (dimatif, thiophosphamide, TEPA, phosphamide, dipin, fotrin), and dichlorethylamine (degranol, IMET). In the group of amidophosphoric acid, "monocentric" mutagens are more active for SCE induction than "polycentric" ones.

Alkylating Agents↗
PubMed1981

[Relation between sister chromatid exchange and duration of human cell treatment with ethyleneimine derivatives].

The sister chromatid exchange (SCE) induction by various concentrations of thiophosphamide and dipin was studied depending on the exposure time to mutagens. There is a linear relationship between the number of SCE and the increase in the concentration and exposure time regardless of the chemical structure of mutagens. The dose dependence (the product of the concentration magnitude by exposure) is also depictable by the linear law. A sudden leap of the number of SCE was observed during the transition from control to minimal exposure.

Antineoplastic Agents↗
PubMed1980

[Effect of long-term exposure to thiophosphamide on the frequency of chromosome aberrations in Chinese hamster cell cultures].

The paper contains the results of the study on the frequency of chromosome aberrations in the cell culture of Chinese hamster under a prolonged action of low concentrations of thiophosphamide (Thph). The frequency of chromosome aberrations in the initial period somewhat increases and then keeps to a certain constant level independently on the duration of action of thiophosphamide. With the heightening of the concentration of the chemical, a sharp increase in the number of chromosome aberrations is observed, which leads to a mass dying of the cell culture. These results may be interpreted as the action of the selection against mutant cells.

Animals↗
PubMed1979

[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↗
PubMed1979

[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↗
PubMed1978

[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↗
PubMed1976

[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↗
PubMed1976

[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↗
PubMed1976

[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↗
PubMed1976

[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↗
PubMed1975

[Anomalies in the karyotypes of premature children].

A cytogenetic investigation of two groups of prematurely born babies was carried out on the basis of the specialized department for prematurely born children in Moscow and in the Moscow Region. The material for this investigation was the culture of lymphocytes. In the first group comprising 607 prematurely born babies without any perceptible developmental defects abnormalities of the karyotype were observed in 15 probands (2.5%) which is 3.5 times higher than the frequency of karyotypic abnormalities among newborn babies from the same population born in proper time. In the second group comprising 70 prematurely born babies with various congenital malformations various karyotypic abnormalities were observed in 13 probands (18,6%), which is 8 times the frequency among babies from the same population born in proper time. The main type of abnormalities observed were those affecting the system of sex chromosomes and the cases of trisomy of the 21st pair of autosomes and structural abnormalities. The high proportion of X- and 21-trisomies among the chromosome abnormalities observed suggests their important role in the etiology of premature births and postnatal death-rate of mutant organisms having D- and E-trisomies and structurally unbalanced chromosomal aberrations.

Chromosome Aberrations↗
PubMed1975

[Mathematical modeling of the relationship between the cytogenetic effect and the concentration of the mutagen].

The effect of different concentrations of thiophosphamide on the culture of human leucocytes was investigated. Three mathematical models were studied, one of which, being satisfactory for describing the experimental data, was chosen. According to this model a quantity of aberrant cells changes with the concentration of thiophosphamide non-linearly and can be described according to the equation A=exp[-(KC+alpha)2], where A is a portion of normal cells, C - a concentration of a mutagen, K and alpha - the coefficients, while exp[-alpha2] is the control level of normal metaphases. The quantity of chromosome breaks per cell is described according to the equation X= exp [KC + +alpha)2]-1. The general view of the equation is constant for different phases of the cell cycle. It follows from the suggested model that the action of two molecules of an alkylating agent is necessary for the formation of a chromosome break. This is indicative of double-stranded structure of a chromosome in its section. It also follows from the suggested model that the action of thiophosphamide has no cut-off. Thiophosphamide induced chromatid aberrations during the G2 phase, therefore it is not a mutagen of the check action.

Cells, Cultured↗
PubMed1975

[The relationship between the cytogenetic effect of thiophosphamide in different concentrations and the temperature of human lymphocytes].

The effect of different concentrations of thiophosphamide on chromosomes of human lymphocytes within 1 hour at the G0 phase under different temperatures was investigated. It is shown that the concentration curves of the effect of thiophosphamide under different temperatures can be described according to the equation: A= =exp [-(KC+alpha)2], X=exp [(KC+alpha)2]-1, where A is the portion of normal cells, X is the number of chromosome breaks per cell, C is the concentration of thiophosphamide, K and alpha are coefficients. The coefficient alpha was shown not to depend on temperature under the action of thiophosphamide on cells. The temperature dependence of the coefficient K can be described according to Arrenius equation: K=A exp [-deltaU/RT]. Proceeding from the experimental data the changes of entropy, free energy and energy of activation of thiophosphamide-chromosome interaction were calculated (deltaS= =18.48 cal-mol-1-degree-1, deltaF310=12897.40 cal-mol-1, deltaU=18626.20 cal-mol-1 for the test "aberrant cells"; deltaS=17.79 cal-mol-1-degree-1, deltaF310=12935.02 cal-mol-1, deltaU= =18449.92 cal-mol-1 for the test "chromosome breaks". These values of thermodynamic potentials show that the reaction of thiophosphamide-chromosome interaction can be of the fermentative nature.

Cells, Cultured↗