Abstract:Adverse health outcomes of ionizing radiation given chronically at low dose rates are highly debated, a controversy also relevant for other stressors. Increased knowledge is needed for a more comprehensive understanding of the damaging potential of ionizing radiation from all dose rates and doses. There is a lack of relevant low dose rate data that is partly ascribed to the rarity of exposure facilities allowing chronic low dose rate exposures. Using the FIGARO facility, we assessed early (one day post-radiati… Show more
“…This study follows the previous descriptions of the animal experiment [ 36 , 47 ]. Specific Pathogen Free CBA/CaOlaHsd (3–8 weeks) mice were purchased from Envigo (Horst, The Netherlands).…”
Section: Methodsmentioning
confidence: 90%
“…Unexposed control mice were housed behind lead shielding outside the radiation field but inside the exposure room. Further details regarding dosimetry and the current experimental design have been described [ 36 , 47 ]. Figure 1.…”
Section: Methodsmentioning
confidence: 99%
“…Gamma radiation was administered using three dose rates (low (LDR), mid (MDR) and high HDR)) to a total dose of 3 Gy. Liver samples were collected for ATAC-Seq (current study) and transcriptional response both early and late (RNA-Seq) [ 36 ]. .…”
Ionizing radiation (IR) impact cellular and molecular processes that require chromatin remodelling relevant for cellular integrity. However, the cellular implications of ionizing radiation (IR) delivered per time unit (dose rate) are still debated. This study investigates whether the dose rate is relevant for inflicting changes to the epigenome, represented by chromatin accessibility, or whether it is the total dose that is decisive. CBA/CaOlaHsd mice were whole-body exposed to either chronic low dose rate (2.5 mGy/h for 54 d) or the higher dose rates (10 mGy/h for 14 d and 100 mGy/h for 30 h) of gamma radiation (
60
Co, total dose: 3 Gy). Chromatin accessibility was analysed in liver tissue samples using Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-Seq), both one day after and over three months post-radiation (>100 d). The results show that the dose rate contributes to radiation-induced epigenomic changes in the liver at both sampling timepoints. Interestingly, chronic low dose rate exposure to a high total dose (3 Gy) did not inflict long-term changes to the epigenome. In contrast to the acute high dose rate given to the same total dose, reduced accessibility at transcriptional start sites (TSS) was identified in genes relevant for the DNA damage response and transcriptional activity. Our findings link dose rate to essential biological mechanisms that could be relevant for understanding long-term changes after ionizing radiation exposure. However, future studies are needed to comprehend the biological consequence of these findings.
“…This study follows the previous descriptions of the animal experiment [ 36 , 47 ]. Specific Pathogen Free CBA/CaOlaHsd (3–8 weeks) mice were purchased from Envigo (Horst, The Netherlands).…”
Section: Methodsmentioning
confidence: 90%
“…Unexposed control mice were housed behind lead shielding outside the radiation field but inside the exposure room. Further details regarding dosimetry and the current experimental design have been described [ 36 , 47 ]. Figure 1.…”
Section: Methodsmentioning
confidence: 99%
“…Gamma radiation was administered using three dose rates (low (LDR), mid (MDR) and high HDR)) to a total dose of 3 Gy. Liver samples were collected for ATAC-Seq (current study) and transcriptional response both early and late (RNA-Seq) [ 36 ]. .…”
Ionizing radiation (IR) impact cellular and molecular processes that require chromatin remodelling relevant for cellular integrity. However, the cellular implications of ionizing radiation (IR) delivered per time unit (dose rate) are still debated. This study investigates whether the dose rate is relevant for inflicting changes to the epigenome, represented by chromatin accessibility, or whether it is the total dose that is decisive. CBA/CaOlaHsd mice were whole-body exposed to either chronic low dose rate (2.5 mGy/h for 54 d) or the higher dose rates (10 mGy/h for 14 d and 100 mGy/h for 30 h) of gamma radiation (
60
Co, total dose: 3 Gy). Chromatin accessibility was analysed in liver tissue samples using Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-Seq), both one day after and over three months post-radiation (>100 d). The results show that the dose rate contributes to radiation-induced epigenomic changes in the liver at both sampling timepoints. Interestingly, chronic low dose rate exposure to a high total dose (3 Gy) did not inflict long-term changes to the epigenome. In contrast to the acute high dose rate given to the same total dose, reduced accessibility at transcriptional start sites (TSS) was identified in genes relevant for the DNA damage response and transcriptional activity. Our findings link dose rate to essential biological mechanisms that could be relevant for understanding long-term changes after ionizing radiation exposure. However, future studies are needed to comprehend the biological consequence of these findings.
“…Эффективность МДР связана в первую очередь с активацией иммунной системы, а также с изменением экспрессии генов, вовлеченных в ответ на действие радиации [3,4]. Рядом авторов были показаны различия в чувствительности к хроническому облучению в малой дозе мышей линий СВА/CA и С57Bl/6.…”
Background: The effects of ionizing radiation (IR) involve a highly orchestrated series of events in cells, including DNA damage and repair, cell death, and changes in the level of proliferation associated with the stage of the cell cycle. A large number of existing studies in literature have examined the activity of genes and their regulators in mammalian cells in response to high doses of ionizing radiation. Although there are many studies, the research in effect of low doses of ionizing radiation remains limited. Though much progress has been made in understanding the basic principles of effects of low doses radiation on individual components of biological systems, less is known about how low doses affect target molecules and regulate the cellular networks (e.g., activation of the immune system, genes and their regulators in the phenomenon of hormesis, the formation of an adaptive response). These observations determined the purpose of the work: to investigate the activity of genes and non-coding RNAs (long non-coding RNAs and microRNAs) in various organs of mice with transplanted Lewis carcinoma after low doses radiation. Material and methods: 24 female mice C57Bl/6 were transplanted subcutaneously with Lewis carcinoma cells (105 cells in 0.2 ml of Hanks’ solution). Total 4-fold X-ray irradiation with an interval of 4 days at a dose of 0.075 Gy (0.85 Gy/min) was performed on the RUST M1 from 6 days after transplantation; the tumor size was measured daily. The mice were divided into the following groups: biocontrol, biocontrol+irradiation, tumor and tumor+irradiation. On the 19th day from the beginning of the experiment, the mice were euthanized. The expression profiles of mRNA genes, long non-coding RNAs and microRNAs controlling the response to radiation were determined in the bone marrow, thymus, spleen and tumor of mice. Results: Fractionated low doses irradiation of mice with transplanted Lewis carcinoma caused a growth decrease of implanted tumour cells compared to the similar group without irradiation. At the same time, there was an activation of oncosuppressors, and a decrease in the activity of oncogenes in the thymus and spleen of mice with tumor and irradiation. In the tumor group, without irradiation, the number of activated oncogenes prevailed over the number of inactivated ones. Conclusion: Thus, the low doses radiation exposure led to the activation of antitumor immunity in mice, which emerged in slowing tumor growth in animals and was represented in the induction of oncosuppressors and inhibition of oncogenes expression.
“…Long-lived 90 Sr (T1/2~29 years) may irradiate the active bone marrow over a long period of time. Adverse health effects of chronic radiation exposure for small mammals are highly debated topic (Fesenko 2019;Dahl et al 2021;Shishkina et al 2021a).…”
Studies of radiobiological effects in murine rodents exposed to internal radiation in the wild or in laboratory experiments require a dosimetric support. The main problem of bone marrow (BM) dosimetry for boneseeking β-emitters is dosimetric modeling due to the fact that the bone is a heterogeneous structure with complex microarchitecture. To date, there are several approaches to calculating the absorbed dose in BM, which mostly use rough geometric approximations. Recently, in the framework of studies of people exposed to 90 Sr in the Urals, a new approach (SPSD) has been developed. The aim of current study was to pilot test the possibility of extension of the SPSD-approach elaborated for humans to mice. The computational phantoms of femur bones of laboratory animals (C57BL/6, C57BL/6J, BALB/c, BALB/cJ) aged 5-8 weeks (growing) and >8 weeks (adults) were created. The dose factors to convert the 89,90 Sr activity concentrations in a bone tissue into units of the dose rate absorbed in the bone marrow were estimated as follows: DFSr-90(BMTBV+CBV) is equal to 1.75±0.42 and 2.57±0.93 (μGy day -1 ) per (Bq g -1 ) for growing and adults, respectively; DFSr-89(BMTBV+CBV) is equal to 1.08±0.27 and 1.66±0.67 (μGy day -1 ) per (Bq g -1 ) for growing and adults, respectively. These results are about 2.5 times lower than skeleton-average DF, calculated assuming the homogenous bone, where source and target coincide. The study demonstrates the possibility of application of the SPSD-approach elaborated for humans to non-human mammals.
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