Low-dose radiobiology program at Canadian nuclear laboratories: past, present, and future

Wang, Yi; Bannister, Laura A.; Sebastian, Soji; Le, Yevgeniya; Ismail, Youssef; Didychuk, Candice; Richardson, Richard B.; Flegal, Farrah; Paterson, Laura C.; Causey, Patrick; Ali, Fawaz; Wyatt, Heather; Priest, Nicholas; Klokov, Dmitry

doi:10.1080/09553002.2018.1562252

Cited by 6 publications

(5 citation statements)

References 70 publications

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“…This, together with the growing use of radiation in medical diagnostics, initiated efforts at national and international levels to support and coordinate radiobiological research with the aim to better understand health effects of low radiation doses. Such research programs were started in several countries (Fukunaga et al 2017;Brooks 2018;Cho et al 2019;Wang et al 2018). In the European Union (EU), radiation protection research is currently being reorganized in an attempt to combine EU funds and national funds from EU member states in an effort to increase the available financial capacity for a better understanding of biological and health effects of low dose radiation (Ruhm et al 2018).…”

Section: Biophysical and Genetic Investigationsmentioning

confidence: 99%

Radiation protection biology then and now

Wójcik

Harms‐Ringdahl

2019

International Journal of Radiation Biology

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Purpose: Radiation biology is a branch of the radiation research field which focuses on studying radiation effects in cells and organisms. Radiation can be used in biological investigations for two, mutually non-exclusive reasons: (1) to study biological processes by perturbing their functioning (qualitative approach) and (2) to assess consequences of radiation-induced damage (quantitative approach). While the former approach has a basic research character, the latter has an applied character that is driven by needs of medical applications and radiological protection. Radiation protection biology is defined in the sense of the second approach. The aim of the article is to provide a historical review of how radiation protection biology developed and how it influences radiological protection. Conclusions: While radiobiological investigations started immediately after the discovery of X-rays, the qualitative approach dominated until the end of World War II. After 1945, the nuclear weapons race and nuclear energy programs initiated quantitative radiobiological research. Radiation protection biology does not provide results from which radiation risks can be directly derived. Rather, it provides data that is necessary for understanding the nature of risks. Most recent years have seen, especially in Europe, a growing interest in coordinated studies on the effects of low radiation doses. ARTICLE HISTORY

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Section: Biophysical and Genetic Investigationsmentioning

confidence: 99%

Radiation protection biology then and now

Wójcik

Harms‐Ringdahl

2019

International Journal of Radiation Biology

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“…ICRP publication 92 indicates that vast majority of neutrons produced by 241 Am-Be are neutrons with 4 MeV energy, and their relative biological effect is 10, meaning their damage capacity is equivalent to 10 times the dose of γ-rays. This highlights the need for further studies on the multiple radiobiological indicators of neutrons ( Neary et al, 1959 ; Broerse et al, 1968 ; Information needed to make radiation, 2006 ; Durante, 2014 ; Little, 2018 ; Wang et al, 2019 ; Holden et al, 2021 ; Wang et al, 2021 ). A wealth of knowledge has been accumulated regarding the radiobiology of neutrons.…”

Section: Introductionmentioning

confidence: 99%

“…A wealth of knowledge has been accumulated regarding the radiobiology of neutrons. Various biological endpoint indicators have been studied in vitro cellular systems, including cell death, pathogenesis, cytogenetic damage, genomic instability, gene expression, mutation, and apoptosis ( Neary et al, 1959 ; Broerse et al, 1968 ; Information needed to make radiation, 2006 ; Durante, 2014 ; Little, 2018 ; Wang et al, 2019 ; Holden et al, 2021 ; Wang et al, 2021 ), all supporting the notion damage is dependent on the radiation dose. It is worth noting that the mixed field of neutrons and γ produced by the 241 Am-Be source may be more detrimental than single radiation.…”

Section: Introductionmentioning

confidence: 99%

Integration of RNA-seq and ATAC-seq analyzes the effect of low dose neutron-γ radiation on gene expression of lymphocytes from oilfield logging workers

Li,

Gao,

Pan

et al. 2023

Front. Chem.

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Objective: Although radiation workers are exposed to much lower doses of neutron-γ rays than those suffered in nuclear explosions and accidents, it does not mean that their health is not affected by radiation. Lower doses of radiation do not always cause morphological aberrations in chromosomes, so more sophisticated tests must be sought to specific alterations in the exposed cells. Our goal was to characterize the specific gene expression in lymphocytes from logging workers who were continuously exposed to low doses of neutron-γ radiation. We hypothesized that the combination of cell type-specific transcriptomes and open chromatin profiles would identify lymphocyte-specific gene alterations induced by long-term radiation with low-dose neutron-γ-rays and discover new regulatory pathways and transcriptional regulatory elements.Methods: Lymphocytes were extracted from workers who have been occupationally exposed to neutron-γ and workers unexposed to radiation in the same company. mRNA-seq and ATAC-seq (Assay for Transposase-Accessible Chromatin with high-throughput sequencing) were performed, followed integrative analysis to identify specific gene regulatory regions induced by neutron-γ radiation. A qPCR assay was then performed to verify the downregulation of RNA coding for ribosomal proteins and flow cytometry was used to detect ribosomal protein expression and cell cycle alterations.Results: We identified transcripts that were specifically induced by neutron-γ radiation and discovered differential open chromatin regions that correlated with these gene activation patterns. Notably, we observed a downward trend in the expression of both differentially expressed genes and open chromatin peaks. Our most significant finding was that the differential peak upregulated in ATAC-seq, while the differential gene was downregulated in the ribosome pathway. We confirmed that neutron-γ radiation leads to transcriptional inhibition by analyzing the most enriched promoters, examining RPS18 and RPS27A expression by qPCR, and analyzing protein-protein interactions of the differential genes. Ribosomal protein expression and cell cycle were also affected by neutron-γ as detected by flow cytometry.Conclusion: We have comprehensively analyzed the genetic landscape of human lymphocytes based on chromatin accessibility and transcript levels, enabling the identification of novel neutron-γ induced signature genes not previously known. By comparing fine-mapping of open chromatin and RNA reads, we have determined that neutron-γ specifically leads to downregulation of genes in the ribosome pathway, with pseudogenes potentially playing a crucial role.

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“…Soon, radiation protection research in Canada centered around Chalk River Laboratories under various federal funding streams, albeit with very limited contribution from other sources (Figure 1). Strikingly, the radiation biology program at Chalk River Laboratories is still in operation today, substantially leveraged by funding from industry, making it the world's longest radiation protection research program (Wang et al 2019). Historically, research in Chalk River at the Atomic Energy of Canada Limited (AECL) has been connected with nuclear industry, via the CANDU reactor technologies.…”

Section: Introductionmentioning

confidence: 99%

“…Subsequently, the radiation protection research program at AECL was supported by the CANDU Owners Group Inc (COG), and such support has undergone a steady growth since 1980s (Figure 1). Importantly, in the late 1990s, COG co-funded the construction of a new animal facility specifically designed for large-scale low-dose radiation studies (Wang et al 2019). This globally unique facility called the biological research facility (BRF) further facilitated low-dose radiation biology studies in Canada, attracting national and international partners and collaborators.…”

Section: Introductionmentioning

confidence: 99%

Funding for radiation research: past, present and future

Cho

Imaoka

Klokov

et al. 2019

International Journal of Radiation Biology

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For more than a century, ionizing radiation has been indispensable mainly in medicine and industry. Radiation research is a multidisciplinary field that investigates radiation effects. Radiation research was very active in the mid-to late 20th century, but has then faced challenges, during which time funding has fluctuated widely. Here we review historical changes in funding situations in the field of radiation research, particularly in Canada, European Union countries, Japan, South Korea, and the US. We also provide a brief overview of the current situations in education and training in this field. A better understanding of the biological consequences of radiation exposure is becoming more important with increasing public concerns on radiation risks and other radiation literacy. Continued funding for radiation research is needed, and education and training in this field are also important.

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Low-dose radiobiology program at Canadian nuclear laboratories: past, present, and future

Cited by 6 publications

References 70 publications

Radiation protection biology then and now

Radiation protection biology then and now

Integration of RNA-seq and ATAC-seq analyzes the effect of low dose neutron-γ radiation on gene expression of lymphocytes from oilfield logging workers

Funding for radiation research: past, present and future

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