The level of spontaneous and radiation-induced DNA damage varies depending on genetic and environmental factors in human somatic cells. This variation may be associated with transcriptional changes in cells, allowing the use of gene expression levels as markers of individual sensitivity to mutagenic effects. This study aimed to identify and characterize differentially expressed genes (DEGs) in lymphocytes of individuals with various frequencies of endogenous γH2AX foci and radiation-induced micronuclei (n = 37). The low-focus group was characterized by 0.18 ± 0.02 endogenous γH2AX foci per cell and a 155.78 ± 47.19‰ radiation-induced micronucleus frequency. The high-focus group was characterized by 0.49 ± 0.07 foci/cell and a 78.44 ± 33.21‰ micronucleus frequency. Seven DEGs (ENST00000424415, CRNDE, ADAMTS1, ENST00000424084, EIF2A, PNPLA5, and FRG2C) (FDR < 0.2) were identified by gene expression analysis with microarrays. As the extracellular matrix metalloproteinase, ADAMTS1 is able to activate the latent form of TGFβ, and TGFβ is involved in radiation-induced cellular response; the effects of ADAMTS1 knockout and overexpression on the gene expression profile were further validated in adherent HeLa cells. Twenty-nine of 160 identified DEGs are involved in apoptosis, DNA DSB repair, G2/M cell cycle transition, and the TGFβ signaling pathway. Thus, ADAMTS1 may be useful as a potential target for antitumor therapy.
The genotoxic effects of exposure to ionizing radiation during the early stages of human embryonic development can be fatal. Despite this, the radiosensitivity of human embryonic and differentiated extraembryonic cells is poorly studied. In this work, the efficiency of a DNA double-strand break repair in human extraembryonic fibroblasts was investigated. It was shown that the repair of radiation-induced DNA damage in human extraembryonic fibroblasts is likely to reflect the ability of these cells to repair spontaneous DNA double-strand breaks.
Effects of ionizing radiation registered in cells after low dose irradiation are still poorly understood. Thus, the aim of this study was to analyze effects of pulsed X-rays on level of radiation-induced DNA double-strand breaks and their repair kinetics in cancer and normalhuman cells in vitro. Analysis of radiation-induced γH2AX and 53BP1 repair foci in MOLT-4 cells with lymphoblastic origin was used for assessment of DNA double-strand breaks (DSB) in these cells. Number of residual radiation-induced γH2AX and 53BP1 foci at 18 hafter irradiation depended on frequency of X-ray pulses: at 8 pulses per second effect was highest in MOLT-4 cells and lowest in peripheral blood lymphocytes. It suggests that pulsed X-rays with various frequencies could be used for target influence on cancer cells being lessdeleterious for normal human cells.
Conclusion:Herein c-Myc acts as a key master regulator of in vitro migration, invasion and radioresistance.In fact, c-Myc depletion alone seems to be sufficient to block the in vitro pro-metastatic abilities and to radiosensitize ERMS cells.In addition, our data suggest c-Myc as important, but not essential, in controlling the molecular machinery responsible for cancer neo-angiogenesis.In conclusion these data strongly suggest that the targeting of c-Myc can be tested as a promising strategy for an anti-cancer therapy.
Фоновый уровень повреждений ДНК и радиочувствительность клеток человека характеризуются значительной межиндивидуальной вариабельностью. Фосфорилирование гистона H2AX ( H2AX) в клетках приводит к включению сигнальной системы, направленной на репарацию двунитевых разрывов ДНК, запуск клеточного старения и активацию контрольных точек клеточного цикла. При этом остается неясной природа фоновых фокусов H2AX и их влияния на клеточную радиочувствительность и эффективность восстановления радиационно-индуцированных повреждений ДНК в клетках человека. В работе у 54 здоровых индивидов проведен анализ связи фонового количества фокусов H2AX в лимфоцитах периферической крови с частотой индуцированных in vitro (2 Гр) центромеро-негативных и центромеро-позитивных микроядер. Обнаружена обратная корреляция между спонтанным количеством фокусов H2AX и уровнем центромеро-негативных микроядер после облучения. Соответствующие корреляции между спонтанным количеством фокусов белка 53BP1 и частотами центромеро-негативных микроядер оказались статистически незначимыми. Кроме того, клетки индивидов с высокой частотой радиационно-индуцированных микроядер характеризовались также низкой пролиферативной активностью. Эндогенные фокусы H2AX представляют собой собранные комплексы, состоящие из белков репарации двунитевых разрывов ДНК и сигнальных медиаторов, участвующих в активации компонентов контрольных точек клеточного цикла. По-видимому, у индивидов с низким спонтанным количеством фокусов H2AX система репарации радиационно-индуцированных двунитевых разрывов ДНК работает менее эффективно и большее число двунитевых разрывов ДНК после воздействия ионизирующего излучения остается нерепарированным. Это приводит как к нарушению клеточного деления в части клеток, так и к потере фрагментов хромосом в виде центромеро-негативных микроядер в ходе митоза в клетках, завершивших деление.
Results of laboratory and field experiments showing the broad use of small amounts of modified carbon nanotubes in agriculture are presented. The effect of modified on the production process of spring wheat variety “Novosibirskaya – 29” in West Siberia was investigated. It was shown that modifications of nanotubes by OH–groups (ethylenediamine) and COOH–groups (ozonation) are promising for the induction of plant resistance to drought and fungal pathogens.
Effects of ionizing radiation registered in cells after low dose irradiation are still poorly understood. Thus, the aim of this study was to analyze effects of pulsed X-rays on level of radiation-induced DNA double-strand breaks and their repair kinetics in cancer and normal human cells in vitro. Analysis of radiation-induced γH2AX and 53BP1 repair foci in MOLT-4 cells with lymphoblastic origin was used for assessment of DNA double-strand breaks (DSB) in these cells. Number of residual radiation-induced γH2AX and 53BP1 foci at 18 h after irradiation depended on frequency of X-ray pulses: at 8 pulses per second effect was highest in MOLT-4 cells and lowest in peripheral blood lymphocytes. It suggests that pulsed X-rays with various frequencies could be used for target influence on cancer cells being less deleterious for normal human cells.