NOTE: Non-targeted effects of ionising radiation

Project summary

The universality of the target theory of radiation-induced effects is challenged by observations on non-targeted effects such as bystander effects, genomic instability and adaptive response. Essential features of non-targeted effects are that they do not require direct nuclear exposure by radiation and they are particularly significant at low doses.

This new evidence suggests a need for a new paradigm in radiation biology. The new paradigm should cover both the classical (targeted) and the non-targeted effects. New aspects include the role of cellular communication and tissue-level responses.

A better understanding of non-targeted effects may have important consequences for health risk assessment and, consequently, on radiation protection. Non-targeted effects may contribute to the estimation of cancer risk from occupational, medical and environmental exposures. In particular, they may have implications for the applicability of the Linear-No-Threshold (LNT) model in extrapolating radiation risk data into the low-dose region.

This also means that the adequacy of the concept of dose to estimate risk is challenged by these findings. Moreover, these effects may provide new mechanistic explanations for the development of non-cancer diseases. Further research is required to determine if these effects, typically measured in cell cultures, are applicable in tissue level, whole animals, and ultimately in humans.

The research efforts needed for understanding the mechanisms involved in non(-DNA) targeted effects and assessing their implications for radiation protection are so large that no single group or country could do this alone. Moreover, a long-term commitment on research in this area will be required even after the 6th framework programme.
We have brought together a multidisciplinary group of scientists representing radiation biology, molecular biology, genetics, immunology, medicine, physics and mathematics from universities and radiation protection authorities to tackle the questions from different scientific perspectives and to evaluate their implication for radiation protection.
In addition to the human resources, we are providing access to a variety of radiobiological infrastructures, such as microbeams, animal irradiation facilities capable of giving protracted doses at low dose rates and facilities for culturing cells in conditions of very low natural radiation background.

Project objectives

• Investigate the mechanisms underlying non-targeted effects
• Investigate if non-targeted effects modulate cancer risk at low doses
• Investigate if ionising radiation can induce non-cancer diseases
• Investigate factors modifying non-targeted responses,
• Assess the relevance of non-targeted effects for radiation protection setting the scientific basis for a modern, more realistic, radiation safety system
• Contribute to the conceptualisation of a new paradigm in radiation biology

Equipment

• Animal facility (at the VITO)
• Genomic platform and other genetic and molecular analysis techniques
• Cell and embryo culture
• Luminex technology for the determination of cytokines and other proteins in serum, plasma, amniotic fluid and human and mouse culture supernatants

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Coordinator

Dr. Sisko Salomaa, Radiation and Nuclear Safety Authority , Finland

Partners

Role	No	Participant name	Short name	Country
CO	1	Radiation and Nuclear Safety Authority	STUK	Finland
CR	2	University of Dundee	UNIVDUN	UK
CR	3	Leipzig University	UL	Germany
CR	4	MRC Radiation and Genome Stability Unit	MRC	UK
CR	5	Imperial College	ICFM	UK
CR	6	Gray Cancer Institute	GCI	UK
CR	7	Belgian Nuclear Research Centre	SCK•CEN	Belgium
CR	8	Dublin Institute of Technology	RESC	Ireland
CR	9	National Institute of Health	ISS	Italy
CR	10	University of Leicester	ULEICS	UK
CR	11	McMaster University	MAC	Canada
CR	12	Atomic Energy of Canada Limited	AECL	Canada
CR	13	National Research Institute for Radiobiology and Radiohygiene	NRIRR	Hungary
CR	14	National Research Centre for Environment and Health	GSF	Germany
CR	15	University of Pavia	UNIPV	Italy
CR	16	University of Erlangen-Nuremberg	FAU	Germany
CR	17	University of Duisburg-Essen	UDE	Germany
CR	18	Norwegian Radium Hospital	RR HF	Norway
CR	19	Ottawa Heart Institute Research Corporation	OHIRC	Canada

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Contact person(s)

Jacquet Paul