RESUMO
Mutagenic character of formaldehyde in vivo was estimated by determining the level of chromosomal aberrations, sister chromatid exchanges and unscheduled DNA synthesis in human lymphocytes. It was found that in case of occupational exposure to formaldehyde the unscheduled DNA synthesis after thiophosphamide treatment in vitro was inhibited and spontaneous level of chromosomal aberrations increased. A negative correlation observed between the unscheduled DNA synthesis and sister chromatid exchanges indirectly confirmed a connection of these exchanges with the DNA repair. The comparison of the results obtained from evaluation of chromosomal aberrations, sister chromatid exchanges and unscheduled DNA synthesis permits suggesting that these methods estimate different sides of the mutagen interaction with a cell and should be considered as mutually complementary methods but not as interchangeable ones.
Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Aberrações Cromossômicas/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Formaldeído/efeitos adversos , Mutagênicos , Troca de Cromátide Irmã/efeitos dos fármacos , Humanos , Linfócitos/ultraestrutura , Testes de MutagenicidadeRESUMO
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.
Assuntos
Bromodesoxicitidina/farmacologia , Bromodesoxiuridina/farmacologia , Troca Genética/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Mitose/efeitos dos fármacos , Troca de Cromátide Irmã/efeitos dos fármacos , Animais , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Fatores de TempoRESUMO
The induction of SCE by fotrine (0.125 and 0.250 microgram/ml) and thiophosphamide (5 micrograms/ml) during the first three cell cycles was studied in the Chinese hamster cells. No increase in the SCE number was observed after treatment with thiophosphamide and fotrine at the G2 stage (the first stage from the moment of fixation) as compared with the control variants. The maximal sensitivity of the cells to the SCE induction by the mutagens is marked at the G1 stage of the first cell cycle before the moment of fixation. The level of SCE remains approximately the same in the second cell cycle before the moment of fixation (20-32 h) and decreased down to the control level at the G1 stage of the third cell cycle (48-52 h).
Assuntos
Ciclo Celular/efeitos dos fármacos , Troca Genética/efeitos dos fármacos , Mutagênicos/farmacologia , Troca de Cromátide Irmã/efeitos dos fármacos , Alquilantes/farmacologia , Animais , Aziridinas/farmacologia , Células Cultivadas , Cricetinae , Cricetulus , Tiotepa/farmacologia , Fatores de TempoRESUMO
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.
Assuntos
Troca Genética/efeitos dos fármacos , Mutagênicos/farmacologia , Troca de Cromátide Irmã/efeitos dos fármacos , Alquilantes/farmacologia , Animais , Células Cultivadas , Células Clonais/efeitos dos fármacos , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Aberrações Cromossômicas , Mutagênicos , Tiotepa/efeitos adversos , Animais , Células Cultivadas , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Mutação , Seleção Genética , Fatores de TempoRESUMO
The method of differential staining of sister chromatids by means of 5-bromdesoxyuridine (BDU) was used to determine duration of the cellular cycle and its phases in a cell culture of Chinese hamster. The mitotic cycle lasted for 16 hrs, G1 for 5 hrs, S for 8 hrs and G2 for 3 hrs. These values do not differ from those obtained by the autoradiography. The given method permits quicker determination of the cellular cycle phases duration as compared with the autoradiography method.
Assuntos
Bromodesoxiuridina/farmacologia , Ciclo Celular/efeitos dos fármacos , Animais , Células Cultivadas , Cricetinae , Cricetulus , Replicação do DNA/efeitos dos fármacos , Coloração e Rotulagem/métodos , Fatores de TempoRESUMO
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.
Assuntos
Células Cultivadas/efeitos dos fármacos , Troca Genética/efeitos dos fármacos , Troca de Cromátide Irmã/efeitos dos fármacos , Tiotepa/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Células Clonais/efeitos dos fármacos , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Interfase/efeitos dos fármacos , Fatores de TempoRESUMO
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.
Assuntos
Bromodesoxiuridina , Cromátides/ultraestrutura , Linfócitos/ultraestrutura , Animais , Células Cultivadas , Células Clonais , Cricetinae , Humanos , Coloração e Rotulagem/métodosRESUMO
Peculiarities of mitotic spiralization of eu- and heterochromatic parts of heteromorphic homologous chromosomes No 1 are investigated. The homologues differ in size of their centromeric heterochromatin segments. In the spiralization range studied (the total lengths of chromosome pair equal to 8.2+25.6 mcm) the lengths of any euchromatic and heterochromatic part change approximately by 3 and 2 times, resp. It is shown that if the chromosome contraction level is not taken into consideration, neither absolute nor relative length of heterochromatic segment can be used for measuring the ratio of heterochromatin. Recommendations for quantitative determination of heterochromatin in chromosome No 1 are given.
Assuntos
Cromossomos Humanos 1-3 , Heterocromatina/ultraestrutura , Humanos , Leucócitos/ultraestrutura , Masculino , Microscopia EletrônicaRESUMO
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.