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

Abstract

Health risks associated with the exposure of humans to low-dose ionizing radiation are currently estimated using the Linear-No-Threshold model. Over the last few decades, however, this model has been widely criticized for inconsistency with a large body of experimental evidence. Substantial efforts have been made to delineate biological mechanisms and health-related outcomes of low-dose radiation. These include a large DOE-funded Low Dose program operated in the 2000s, as well as the EU funded programs, previously NOTE and DOREMI and currently MELODI. Although not as widely known, the Atomic Energy of Canada Limited (AECL) in Chalk River, operated a low-dose radiobiology program since as early as 1948. The Canadian Nuclear Laboratories (CNL), the successor to AECL since 2015, has expanded this program into new areas making it the world’s most robust, centrally coordinated and long-lived research efforts to delineate the biological effects of low-dose radiation. The purpose of this review is to provide a high-level overview of the low-dose radiobiology program maintained at CNL while capturing the historical perspectives. Past studies carried out at CNL have substantially influenced the area of low-dose radiobiology, exemplified by highly cited papers showing delays in spontaneous tumorigenesis in low-dose irradiated mice. The current low-dose research program at CNL is not only addressing a wide range of mechanistic questions about the biological effects of low doses - from genetic to epigenetic to immunological questions - but also moving toward novel areas, such as the dosimetry and health consequences of space radiation and the use of low-dose radiation in cancer therapy and regenerative medicine.

Keywords:

• Low doses
• ionizing radiation
• health effects
• cancer risks
• Canadian Nuclear Laboratories
• Chalk River

Acknowledgments

The authors are grateful to all technologists who have helped with the studies mentioned in this review. Support of the Biological Research Facility team is greatly appreciated.

Disclosure statement

No potential conflict of interest reported by the authors.

Additional information

Funding

Current radiobiological studies are financially supported by the CNL’s Federal Science and Technology program and CANDU Owners Group. Past funding organizations include the Canadian Nuclear Safety Commission, Health Canada, the EU 7th Framework Program.

Notes on contributors

Yi Wang

Yi Wang, PhD in Cell Biology and MB (MD equivalent) in Clinical Medicine, is currently a Scientist of Radiobiology section at Canadian Nuclear Laboratories and an Adjunct Professor at the Department of Biochemistry, Microbiology and Immunology of University of Ottawa. His research interests lie broadly in various areas of Radiobiology, with a strong interest on low dose radiation therapy.

Laura A. Bannister

Laura A. Bannister, PhD in Biochemistry and Molecular Biology, is an R&D Scientist at Canadian Nuclear Laboratories and an Adjunct Professor at the Department of Biochemistry, Microbiology and Immunology of University of Ottawa. Her current research interests are on the effects of low-dose ionizing radiation (from medical, occupational and environmental exposures) on human cancer and non-cancer diseases.

Soji Sebastian

Soji Sebastian, PhD in Cell Biology, is currently a research scientist in the Radiobiology and Health Branch at Canadian Nuclear Laboratories (CNL). Dr. Sebastian has been in the field of muscle stem cell biology and gene expression using next generation sequencing technologies to address epigenetic basis of tissue regeneration. At CNL, Dr. Sebastian is investigating the epigenetic effects of ionizing radiation in cardiac and skeletal muscle. Experimental approaches span from molecular in vitro studies to integrative in vivo stem cell biology and mass spectrometry.

Yevgeniya Le

Yevgeniya Le, PhD in Pathology and Laboratory Medicine and undertook Postdoctoral Training in hematology, stem cell biology and radiobiology. She is currently a Scientist with Canadian Nuclear Laboratories and an Adjunct Professor in the Department of Biochemistry, Microbiology and Immunology at the University of Ottawa. Her research interests are in stem cell and cancer research with a focus on low dose radiation exposures.

Youssef Ismail

Youssef Ismail, PhD Biological Sciences from the University of Montreal (Université de Montréal), Canada. Former Scientist at Canadian Nuclear Laboratories (CNL), Chalk River, Ontario. His research at CNL focused on investigating biological effects of low-dose ionizing radiation in mammalian cells with particular focus on DNA damage and repair. Currently, he is an R&D Facilities Specialist at CNL supporting nuclear facilities and radioisotope laboratories to ensure compliance with Canadian Nuclear Safety Commission regulations for implementing operational safety, reliability and efficiency.

Richard B. Richardson

Dr. Richard B. Richardson, obtained a degree and masters degree from the Universities of London and Aberdeen. He worked as a medical physicist and researcher into brain tumour therapies using monoclonal antibodies. For his University of Bristol PhD, he assessed the risk of leukaemia for natural radon gas. He has published extensively on tritium and 14C, and realistic dosimetric/oxygen models for coronary arteries and bone remodelling. In addition, his research explores the mechanisms whereby p53 mutations, radiation or infections induce cancer, but also the role of stem cell senescence and its parallel relationship with aging. Currently he is a section head and principal investigator at Canadian Nuclear Laboratories (CNL), Chalk River, Ontario, Canada carrying out collaborative research into the radiation quality of neutrons with the McGill Medical Physics Unit in Montreal. He also works on understanding radiation-induced oxidative stress, radiation-induced cataracts and identifying radon biomarkers with collaborators at the University of Ottawa and University of Calgary. Dr. Richardson is an adjunct professor of McGill University and has authored 75 peer-reviewed articles.

Laura C. Paterson

Laura C. Paterson, Senior Technologist at Canadian Nuclear Laboratories (CNL), Chalk River, Canada. She holds a MSc in Radiation Sciences from McMaster University, Canada, and is pursuing a PhD in Experimental Medicine at McGill University, Canada. Laura is currently investigating the biological effects of secondary neutrons generated during cancer radiotherapy and has published on biological effects, such as chromosomal damage and cell death, following thermal neutrons exposures of human lymphocytes. She also assists with CNL’s biodosimetry programme and provides support to research addressing radiation-induced cataracts.

Patrick Causey

Patrick Causey, PhD in Chemistry, is currently a Research Scientist at Canadian Nuclear Laboratories. He received his degree from Queen’s University, working with Professor Mike Baird, before completing a Post-Doctoral Fellowship with John Valliant at McMaster University. Prior to starting with CNL, he worked for the Centre for Probe Development and Commercialization. His research interests lie broadly in areas of radiochemistry, radiopharmacy and medicinal chemistry, with a focus on developing new tracers for imaging and therapy of cancer.

Ali Fawaz

Ali Fawaz, PhD in Nuclear Engineering with a specialization in Radiological and Health Physics, is a physicist in the Radiobiology and Health branch at Canadian Nucle Laboratories. His research interests are in radiation detection, radiation dosimetry, and in Monte Carlo simulations for radiation transport calculations.

Heather Wyatt

Heather Wyatt, DVM, is currently semi-retired from the Radiobiology and Health branch at Canadian Nuclear Laboratories. She was the veterinary advisor for the Radiobiology section of the aforementioned branch from 1988 to 2018.

Nicholas Priest

Nicholas Priest, PhD, Medicine. Retired. Former manager of radiobiology at Chalk River, Canada and Harwell. UK. Professor of Radiobiology and Environmental Science at Middlesex University, London. His research interests include the metabolism, dosimetry and toxicity of radioactive and stable nuclides.

Dmitry Klokov

Dmitry Klokov, PhD in Radiobiology, currently he is a head of Radiobiology section at Canadian Nuclear Laboratories and an Adjunct Professor at the Department of Biochemistry, Microbiology and Immunology of University of Ottawa. His research interests lie broadly in various areas of Radiobiology, with a focus on low doses.