[Effect of duration and number of cell cycles after mutagenic exposure on the frequency of sister chromatid exchange].
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Biomedical subjects
Publications and source records attributed to S M Kuzin.
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The dynamics of sister chromatid exchanges and chromosome aberrations in lymphocyte of monkey has been investigated after a thiophosphamide exposure. The process of induction and elimination of cytogenetic damages was described by the mathematical model. Developing the model in detail will allow to make a cytogenetic prognosis of remote consequences of mutagenic exposure.
Mutagenic in vivo and in vitro effects were compared quantitatively by the investigation of sister chromatid exchange (SCE) rate and chromosomal aberrations caused by thiophosphamide in macaca rhesus lymphocytes. The integral of thiophosphamide concentration in the blood or culture fluid by a certain time period was used for the estimation of the dose of mutagenic exposure. It was shown that the dose-response relationships and corresponding regression coefficients were similar when the in vivo and in vitro results were compared. The data obtained indicate the possibility for quantitative extrapolation of the results obtained in vitro on the entire organism.
Cyclophosphamide (CP) and its metabolites were used to compare the rate of chromosomal aberrations (CA) and sister chromatid exchange (SCE) in the rabbit lymphocytes in vivo and in vitro. The dose-dependent increase of cytogenetic effects rate appeared to be of linear and exponential dependence for SCE and CA, respectively, both in vivo and in vitro. The regression equation coefficients coincided in in vivo and in vitro experiments.
The comparative in vivo and in vitro study of chromosomal aberrations and SCE induced by cyclophosphamide (CP) in macaca rhesus lymphocytes was performed. The dose of mutagenic exposure for quantitative estimation of effects was determined as a product of concentration of alkylating CP metabolites on the exposure time. The mutagenic effect caused by the same doses of CP (CP metabolites) appeared similar in vivo and in vitro. This suggests that the results obtained in adequate in vitro mutagen-testing experiments may be quantitatively extrapolated for the in vivo conditions.
The dose dependences of chromosome aberrations rate were investigated in lymphocytes of oncological patients after cyclophosphamide (CP) administration. It was shown that the rate of chromosome aberrations and the number of disruptions per cell in vivo and in vitro increases exponentially with the dose. At the same time, the parameters of regression equations coincide. This evidences that CP has the similar effect in vivo and in vitro.
Parameters of the cell mitotic cycle (MC) in the esophageal epithelium of mice were studied 5, 10 and 17 days after inverting the light schedule (light from 8 a. m. to 8 p. m. in the control group, L : D = 12:12, and light from 8 p. m. to 8 a. m. in the experimental one., L : D = 12:12). The duration of different MC periods is similar in the control and experimental animals at varying time after inversion of the light schedule: G2min- 1.0-2.0 h, G2 + 1/2M = 2.0 -2.7 h, S = 7.1-7.7 h, G1 + 1/2M = 14.0-15.5 h. The total MC duration is 24-25 h. The pattern of the labeled mitotic curves after inversion only slightly differs from the control. This is evidence of stability of MC cell kinetics after inversion of the light schedule. The intracyclic regulatory mechanisms appear not to be affected essentially by this inversion.
Circadian rhythms of the mitotic activity, DNA synthesis and the parameters of the mitotic cells of the mouse esophagus epithelium were studied during the periods of maximum and minimum proliferation. The number of mitoses and DNA-synthetizing cells increases rhythmically at 1--7 a. m. from 22 p. m. to 4 a. m., respectively. When 3H-thymidine was injected to the mice at 2 a. m., tG2min was 1h; tG2+1/2 M was 2h; tS was 7.1; tG1+1/2 M was 2h; tS was 7.1; tG1+1/2 M was 15.9h. When 3H-thymidine was injected at 2 p. m., tS rose up to 8.2 and tG1+1/2 M up to 14.8h. The mitotic cycle in both series of experiments totalled 25 h. Thus, the duration of various phases of the mitotic cycle depends on the time of the day and correlates with circadian rhythms of the mitotic activity and the number of DNA-synthetizing cells. Duration of the mitotic cycle of the cells passing through it at varying time of the day is the same and approximates the period of the circadian rhythm of mitoses and DNA synthesis in esophagus epithelium.
A comparative study of cytogenetic effects in human lymphocytes caused in vivo by cyclophosphamide (CP) after intravenous injection and in vitro by exposure of plasma of the same patients was carried out. It was found that the frequency of induced chromosome aberrations (CA) and sister-chromatid exchanges (SCE) increased linearly for SCE and exponentially for CA within the 'dose' of alkylating activity of CP metabolites. Parameters of 'cytogenetic effect-dose' in vivo and in vitro coincided. The intensity of cytogenetic effects varied between individuals.