Ionizing radiation biomarkers for potential use in epidemiological studies.
Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100mSv and/or 0.1mSvmin(-1)) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of potential confounding factors, are also essential.
Centre for Research in Environmental Epidemiology (CREAL), Radiation programme, IMIM (Hospital del Mar Research Institute) and CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona Biomedical Research Park (PRBB), Doctor Aiguader, 88, 08003 Barcelona, Spain. Electronic address: epernot@creal.cat.
Eileen
E
Pernot
Institut Curie, Inserm U612, Centre Universitaire, Bats 110-112, Orsay 91405, France.
Janet
J
Hall
Belgian Nuclear Research Center (SCK-CEN), Boeretang 200, BE-2400 Mol, Belgium; University of Gent, BE-9000 Gent, Belgium.
Sarah
S
Baatout
Belgian Nuclear Research Center (SCK-CEN), Boeretang 200, BE-2400 Mol, Belgium.
Mohammed Abderrafi
MA
Benotmane
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Internal Dosimetry Department, 31 avenue de la Division Leclerc, 92260 Fontenay-aux-Roses, France.
Eric
E
Blanchardon
Health Protection Agency (HPA), Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxfordshire OX11 0RQ, UK.
Simon
S
Bouffler
Belgian Nuclear Research Center (SCK-CEN), Boeretang 200, BE-2400 Mol, Belgium; University of Gent, BE-9000 Gent, Belgium.
Houssein
H
El Saghire
Federal Office for Radiation Protection, Department Radiation Protection and Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
Maria
M
Gomolka
Federal Office for Radiation Protection, Department Radiation Protection and Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
Anne
A
Guertler
Centre for Radiation Protection Research (CRPR), Department of Genetics, Microbiology and Toxicology, Stockholm University, SE 106 91 Stockholm, Sweden.
Mats
M
Harms-Ringdahl
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, BN1 9QG, UK.
Penny
P
Jeggo
Federal Office for Radiation Protection, Department Radiation Protection and Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
Michaela
M
Kreuzer
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Radiobiology and Epidemiology Department, 31avenue de la Division Leclerc, 92260 Fontenay-aux-Roses, France.
Dominique
D
Laurier
Radiation and Nuclear Safety Authority, Laippatie 4, 00880 Helsinki, Finland.
Carita
C
Lindholm
Commissariat à l'Énergie Atomique (CEA), Laboratoire de Radiobiologie et Oncologie (LRO), 18, Route du Panorama - BP6, 92265 Fontenay-aux-Roses, France.
Radhia
R
Mkacher
Belgian Nuclear Research Center (SCK-CEN), Boeretang 200, BE-2400 Mol, Belgium.
Roel
R
Quintens
Health Protection Agency (HPA), Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Didcot, Oxfordshire OX11 0RQ, UK.
Kai
K
Rothkamm
Commissariat à l'Énergie Atomique (CEA), Laboratoire de Radiobiologie et Oncologie (LRO), 18, Route du Panorama - BP6, 92265 Fontenay-aux-Roses, France.
Laure
L
Sabatier
Helmholtz Zentrum München (HGMU), German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, D-85764 Neuherberg, Germany.
Soile
S
Tapio
Institut National de la Santé et de la Recherche Médicale (INSERM), U1018, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif cedex, France.
Florent
F
de Vathaire
Centre for Research in Environmental Epidemiology (CREAL), Radiation programme, IMIM (Hospital del Mar Research Institute) and CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona Biomedical Research Park (PRBB), Doctor Aiguader, 88, 08003 Barcelona, Spain. Electronic address: ecardis@creal.cat.
Elisabeth
E
Cardis
D015415:Biomarkers; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004249:DNA Damage; D016021:Epidemiologic Studies; D044127:Epigenesis, Genetic; D006801:Humans; D055432:Metabolomics; D017720:Molecular Epidemiology; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species
D015415:Biomarkers; D017382:Reactive Oxygen Species