Kinetics of DNA Repair Under Chronic Irradiation at Low and Medium Dose Rates in Repair Proficient and Repair Compromised Normal Fibroblasts

We present time and dose dependencies for the formation of 53BP1 and γH2AX DNA damage repair foci after chronic radiation exposure at dose rates of 140, 250 and 450 mGy/day from 3 to 96 h, in human and mouse repair proficient and ATM or DNA-PK deficient repair compromised cell models. We describe the time/dose-response curves using a mathematical equation which contains a linear component for the induction of DNA damage repair foci after irradiation, and an exponential component for their resolution. We show that under conditions of chronic irradiation at low and medium dose rates, the processes of DNA double-strand breaks (DSBs) induction and repair establish an equilibrium, which in repair proficient cells manifests as a plateau-shaped dose-response where the plateau is reached within the first 24 h postirradiation, and its height is proportionate to the radiation dose rate. In contrast, in repair compromised cells, where the rate of repair may be exceeded by the DSB induction rate, DNA damage accumulates with time of exposure and total absorbed dose. In addition, we discuss the biological meaning of the observed dependencies by presenting the frequency of micronuclei formation under the same irradiation conditions as a marker of radiation-induced genomic instability. We believe that the data and analysis presented here shed light on the kinetics of DNA repair under chronic radiation and are useful for future studies in the low-to-medium dose rate range.

Effects of genomic instability in populations of Drosophilae melanogaster from regions of Ukraine with different radiation impact factors

Differences in the gonadal dysgenesis frequency as an indicator of the activation of mobile elements were revealed in F1-descendants of natural populations of Drosophіla melanogaster, selected from regions of different radiation impact. Under conditions of additional low-rate chronic irradiation in laboratory conditions for 10 generations, significant differences in changes in the level and dynamics of this indicator were established depending on the accumulated dose of Drosophila populations from the city of Netishin (Khmelnytskyi NPP) and Magarach city.

Effects of Acute and Chronic Gamma Irradiation on the Cell Biology and Physiology of Rice Plants

The response to gamma irradiation varies among plant species and is affected by the total irradiation dose and dose rate. In this study, we examined the immediate and ensuing responses to acute and chronic gamma irradiation in rice (Oryza sativa L.). Rice plants at the tillering stage were exposed to gamma rays for 8 h (acute irradiation) or 10 days (chronic irradiation), with a total irradiation dose of 100, 200, or 300 Gy. Plants exposed to gamma irradiation were then analyzed for DNA damage, oxidative stress indicators including free radical content and lipid peroxidation, radical scavenging, and antioxidant activity. The results showed that all stress indices increased immediately after exposure to both acute and chronic irradiation in a dose-dependent manner, and acute irradiation had a greater effect on plants than chronic irradiation. The photosynthetic efficiency and growth of plants measured at 10, 20, and 30 days post-irradiation decreased in irradiated plants, i.e., these two parameters were more severely affected by acute irradiation than by chronic irradiation. In contrast, acutely irradiated plants produced seeds with dramatically decreased fertility rate, and chronically irradiated plants failed to produce fertile seeds, i.e., reproduction was more severely affected by chronic irradiation than by acute irradiation. Overall, our findings suggest that acute gamma irradiation causes instantaneous and greater damage to plant physiology, whereas chronic gamma irradiation causes long-term damage, leading to reproductive failure.

The role of jasmonate signaling pathway in plant’s flowering genes response to ionizing radiation

Aim. This study aimed to characterize the role of the jasmonate signaling pathway in flowering genes response to acute and chronic ionizing irradiation in plants. Methods. We used the wild-type Arabidopsis thaliana and jasmonic pathway defective jin mutant of Col0 ecotype in our experiments. The chronic irradiation was provided by 137СsCl with a total dose of 17 cGy and a dose rate of 6.8×10-6 cGy/s. The acute irradiation experiment was performed on 21 days old plants at the 5.0 stage (Boyes 2001) by X-rays in a total dose of 5 Gy with a dose rate of 89 cGy/s. The length of stems and leaves was measured in post-irradiation period. The molecular genetic analysis was done using real-time PCR. We determined the relative expression of key flowering genes AP1, GI, FT, CO, ACT2 with UBQ10 used as reference genes. Statistical analysis of phenotypic parameters was done using Student’s t-test in GraphPad Prism 8 software. The quantitative PCR data were analyzed in the REST 2009 software, QIAGEN. Results. The plant groups differed significantly by the stem length (p>0,05). The study revealed decreased expression of CO, GI and FT genes in jin mutants. The overexpression of AP1 in jin mutants under chronic irradiation may cause cell division errors and impact flower development. In contrast, AP1 expression in WT plants was near to normal =1 under chronic irradiation. These results suggest the involvement of the jasmonate pathway in the regulation of plants flowering during the irradiation. Сonclusion. Based on the results of our study, we hypothesize that jasmonic acid has a stabilizing effect on the rate of cell differentiation in plants under chronic irradiation. Despite the uncovered role of jasmonic acid in Arabidopsis thaliana flowering the exact mechanism of its action remains unclear and requires further investigation.Keywords: jasmonate signaling, jasmonic acid, JA, flowering, ionizing radiation, real-time PCR, relative expression.

Chronic irradiation with low-dose-rate 137Cs-γ rays inhibits NGF-induced neurite extension of PC12 cells via Ca2+/calmodulin-dependent kinase II activation

Chronic irradiation with low-dose-rate 137Cs-γ rays inhibits the differentiation of human neural progenitor cells and influences the expression of proteins associated with several cellular functions. We aimed to determine whether such chronic irradiation influences the expression of proteins associated with PC12 cells. Chronic irradiation at 0.027 mGy/min resulted in inhibition of NGF-induced neurite extension. Furthermore, irradiation enhanced the nerve growth factor (NGF)-induced increase in the phosphorylation of extracellular signal–regulated kinase (ERK), but did not affect the phosphorylation of NGF receptors, suggesting that irradiation influences pathways unassociated with the activation of ERK. We then examined whether irradiation influenced the Akt−Rac1 pathway, which is unaffected by ERK activation. Chronic irradiation also enhanced the NGF-induced increase in Akt phosphorylation, but markedly inhibited the NGF-induced increase in Rac1 activity that is associated with neurite extension. These results suggest that the inhibitory effect of irradiation on neurite extension influences pathways unassociated with Akt activation. As Ca2+/calmodulin-dependent kinase II (CaMKII) is known to inhibit the NGF-induced neurite extension in PC12 cells, independent of ERK and Akt activation, we next examined the effects of irradiation on CaMKII activation. Chronic irradiation induced CaMKII activation, while application of KN-62 (a specific inhibitor of CaMKII), attenuated increases in CaMKII activation and recovered neurite extension and NGF-induced increases in Rac1 activity that was inhibited by irradiation. Our results suggest that chronic irradiation with low-dose-rate γ-rays inhibits Rac1 activity via CaMKII activation, thereby inhibiting NGF-induced neurite extension.

Differences in sustained alterations in protein expression between livers of mice exposed to high-dose-rate and low-dose-rate radiation

Molecular mechanisms of radiation dose-rate effects are not well understood. Among many possibilities, long-lasting sustained alterations in protein levels would provide critical information. To evaluate sustained effects after acute and chronic radiation exposure, we analyzed alterations in protein expression in the livers of mice. Acute exposure consisted of a lethal dose of 8 Gy and a sublethal dose of 4 Gy, with analysis conducted 6 days and 3 months after irradiation, respectively. Chronic irradiation consisted of a total dose of 8 Gy delivered over 400 days (20 mGy/day). Analyses following chronic irradiation were done immediately and at 3 months after the end of the exposure. Based on antibody arrays of protein expression following both acute lethal and sublethal dose exposures, common alterations in the expression of two proteins were detected. In the sublethal dose exposure, the expression of additional proteins was altered 3 months after irradiation. Immunohistochemical analysis showed that the increase in one of the two commonly altered proteins, MyD88, was observed around blood vessels in the liver. The alterations in protein expression after chronic radiation exposure were different from those caused by acute radiation exposures. Alterations in the expression of proteins related to inflammation and apoptosis, such as caspase 12, were observed even at 3 months after the end of the chronic radiation exposure. The alterations in protein expression depended on the dose, the dose rate, and the passage of time after irradiation. These changes could be involved in long-term effects of radiation in the liver.