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OBJECTIVE: To study the frequency and spectrum of chromosome aberrations in human peripheral blood lymphocytes depending on the radiation dose, the stage of the mitotic cycle and the periods of fixation of the cell culture. MATERIALS AND METHODS: The test system of blood lymphocytes of donors, the metaphase analysis of chromosome aberrations (a uniform staining of the drugs). The gamma-irradiation was performed on the device with the source 60Co at the dose rate of 0.5 Gy/min, the dose range was 0.25-4.0 Gy. The lymphocyte culture was irradiated after 0, 24, 40 and 48 hours from the beginning of the incubation, which corresponds to G0-, G1-, S-, G2-stages of the mitot- ic cycle. The cells were fixed after 52 hours and 62 hours from the beginning of the incubation. RESULTS: The author's experimental data on the regularities of chromosome aberrations formation during irradiation at the different periods of the mitotic cycle of human lymphocyte culture are presented. The character of the dose dependences of structural damages of chromosomes during the mitotic cycle with an application of the linear, lin- ear-square and parabolic models is analyzed. The greatest yield of exchange-type aberrations is registered at the irradiation in G0- and G1-stages of the mitotic cycle, which submits to the linear-square dependence on an irradia- tion dose. When irradiating cells in the S- and G2-stages, the main contribution to the spectrum of radiation-induced chromosome aberrations is made by deletions, the level of which increases linearly with the dose. This is evidenced by the negative values of the quadratic term in the regression equations for these stages. The analysis of the curves using the parabolic model Y = k · Dn has shown that, at the irradiation of lymphocytes in G0- and G1-stages, the dose dependences approach the quadratic ones, which confirms the reasonableness of the interpretation of the obtained cytogenetic data from the point of view of the «classical¼ theory of the radiation-induced chromosome aberrations formation. However, the model of the spline regression is more accurate at the approximation of the dependences of the cytogenetic effects in the region of low doses of irradiation. CONCLUSIONS: The results obtained by the irradiation of human lymphocyte culture at different stages of the mitot- ic cycle indicate that the same radiation dose induces different qualitative and quantitative cytogenetic effects depending on the physiological state of the cell at the time of irradiation. The combination of such factors as a radi- ation dose rate, a mitotic cycle stage, the post-irradiation conditions, and an individual radiosensitivity are reflect- ed in quantitative and qualitative variations of the cellular radiosensitivity.

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Using the autoradiographic method, we studied the kinetics of DNA synthesis over the mitotic cycle in mouse corneal epithelium cells in delayed periods after γ-irradiation in different points of the S phase of the first mitotic cycle. The index labeled cells during 1-3 periods of DNA synthesis most adequately reflects quantitative changes in the cell population composition after cell exposure during the first S period. The relative number of labeled S phase cells in the second mitotic cycle in experiments where the cells were irradiated in the S1 phase of the first S period was 4-fold lower than in experiments where the cells were exposed during S2 phase. This effect is determined by inhibition of the transcription factors activation. It seems that two territorially different sites of the genome controlling the regulatory stimuli and involved in modification of the quantitative composition of the population are responsible for changes in its quantitative balance.

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Kinetics of DNA synthesis throughout the mitotic cycle in mouse corneal epithelial cells after single γ-irradiation of cells (4 Gy) at the end of S phase was studied by the method of radioautography. It was found that single irradiation increased the duration of S phase due to reparation of damage in the cell at the expense of time that normally falls on g1 phase. During reparation, two parallel DNA synthesis processes occur in the damaged cells: de novo synthesis at the site of injury after excision of the damaged fragments (reparative synthesis) and supplementary synthesis during the repair period in the remaining undamaged genome competent for replication. During supplementary synthesis, repeats appear in DNA structure, which increases the amount of genetic material in the cell and affect S phase duration. All reparative processes take place in the cell population consisting of subpopulations of "differentiated", "resting", and "proliferating" cells. The changes in the proportions between the subpopulations under the influence of extreme factors can induce the appearance of metastatic cells in the population.

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The paper summarizes literature data on the importance of oxidative stress as one of the pathogenetic mechanisms in Alzheimer's disease. The paper describes the main specific and nonspecific ways of reactive oxygen species generation in the course of the disease development. The effect of reactive oxygen species generated by the functional activity of cells, i.e. apoptosis and mitotic cycle, is shown. The role of the regulatory system of nodal cells is performed by phosphorylation/dephosphorylation process which is associated with intense phosphorylation of tau protein and mitosis-specific proteins. In Alzheimer's disease, the regulating function of peptidyl-prolyl isomerases in particular of Pin1 associated with maintaining a balanced state of phosphorylation/dephosphorylation processes is disturbed. Taking into consideration the multifactorial impairment of the cell cycle control, this process should be considered from the standpoint of the general state of metabolic processes, and oxidative stress has one of the key positions in aging.

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During Drosophila oogenesis, activation of Notch signaling in the follicular epithelium (FE) around stage 6 of oogenesis is essential for entry into the endocycle and a series of other changes such as cell differentiation and migration of subsets of the follicle cells. Notch induces the expression of zinc finger protein Hindsight and suppresses homeodomain protein Cut to regulate the mitotic/endocycle (ME) switch. Here we report that broad (br), encoding a small group of zinc-finger transcription factors resulting from alternative splicing, is a transcriptional target of Notch nuclear effector Suppressor of Hairless (Su(H)). The early pattern of Br in the FE, uniformly expressed except in the polar cells, is established by Notch signaling around stage 6, through the binding of Su(H) to the br early enhancer (brE) region. Mutation of the Su(H) binding site leads to a significant reduction of brE reporter expression in follicle cells undergoing the endocycle. Chromatin immunoprecipitation results further confirm Su(H) binding to the br early enhancer. Consistent with its expression in follicle cells during midoogenesis, loss of br function results in a delayed entry into the endocycle. Our findings suggest an important role of br in the timing of follicle cell development, and its transcriptional regulation by the Notch pathway.

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Nuclei have been isolated from plasmodia ofPhysarum. Chromatin has been prepared from these nuclei by lysing them gently with lysolecithin. Both nuclei and chromatin contain endogenous activities of RNA polymerases A and C but not of RNA polymerase B under the conditions specifiied. RNA synthesis of chromatin and nuclei can be stimulated by the addition of purified RNA polymerases. RNA polymerase B is significantly more active than A or the bacterial RNA polymerase fromEscherichia coli. Experiments with specific inhibitors indicate that this additional RNA transcription is due to initiation by exogenously supplied RNA polymerase B. Large RNA products (up to 30 S when analysed under denaturating conditions) are transcribed on chromatin.The template activity of nuclei or chromatin, measured using saturating amounts of added RNA polymerase B, correlates with the in vivo RNA synthesis in three well defined situations. It decreases during starvation when the plasmodium prepares for encystment and is very low during mitosis, however, it is very high during the S-phase of the mitotic cycle when the highest activity of poly(A) + RNA synthesis is detected.

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The rate of the first four cleavage divisions has been investigated in 8 teleost species. A comparison of cytological studies of the duration of the mitotic cycle in four species with visual observations on the intervals between the appearance of furrows of the first four cleavage divisions in the same species at the same temperatures has shown that in teleosts the duration of the mitotic cycle during synchronous cleavage divisions ({ie301-1} equals one half of the time period between the appearance of furrows of the 2nd and 4th cleavage divisions. At optimal temperatures, it also corresponds to 1/5 of the period between insemination and the appearance of the 1st cleavage furrow. Using these two method, {ie301-2} values were calculated in the species under study for a wide temperature range and curves of the temperature-dependence of {ie301-3} were constructed. Temperatures below the spawning temperature range produced a shortening of the relative duration (in terms of {ie301-4} units) of the period between insemination and the appearance of the 1st cleavage division furrow, as well as a shift in temporal relationships between the successive mitotic phases: the relative duration of the active mitotic phases (especially metaphase) decreased sharply while the overall relative duration of telo-, inter-and prophase increased correspondingly. On the basis of the results obtained the question of the determination of the lower limit of the optimal temperature range in teleosts is discussed.