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Non-nuclear energy

RISC-RAD

Fission and radiation protection
Fusion
   

Quantification of Risks Associated with Low and Protracted Doses

Using innovative technologies for the identification of genetic variables in the processing of radiation damage and quantitative analysis of the implications for risk assessment, RISC-RAD gathers together the full spectrum of European research in radiobiology from DNA damage to cancer induced by ionising radiation, and modelling for the improvement of quantitative risk assessment of the effects of low and protracted exposure to radiation.


Understanding low dose effects

Effective radiation protection requires a thorough understanding of the effects of low doses of ionising radiation. Currently, the effects of low doses are extrapolated from our knowledge of the effects of high doses. In addition, it is important to appreciate the variation in individual responses to radiation within the human population due to genetic factors.

Present estimates of the risks from radiation exposure are based largely on the ‘average’ individual in an exposed population. However, clinical observations of adverse reactions to radiotherapy indicate that large variations exist in radio-sensitivity. RISC-RAD will improve the quantification of risks by identifying all the relevant parameters that determine the differences in response to radiation. Underlying this study is an essential need to assemble a detailed knowledge of the mechanisms by which radiation interacts with cells and genetic material to induce cancer in humans.

Elements of the RISC-RAD project (Courtesy: CEA)
Elements of the RISC-RAD project (Courtesy: CEA)

Radio-biological interactions, genetic variation

RISC-RAD is coordinated by CEA in France and encompasses a multidisciplinary team from 33 laboratories involved in radiobiology, genetics, molecular biology, cellular biology, biophysics and oncology, using an array of innovative and state-of-the-art technology (genomics, proteomics, advanced fluorescence microscopy, RNA interference, gene knock-in technology). Five specific activities will be undertaken. The defensive response of DNA to damage by radiation will be investigated including the impact of the major defence pathways (DNA repair, cell cycle checkpoints, apoptosis) and radio-sensitivity using in vitro models and living cells. How genomic instability, including the role of ageing and other structural effects, is associated with the development or otherwise of cancer cells will be studied as will the actual mechanisms of tumourigenesis triggered by radiation, including the effects of radiation-induced mutations. Genetic susceptibility to radiogenic tumours will be researched involving the complexity of common genetic determinants, how tumours respond and are suppressed, and the intra-variation in human radiation response. Finally, the mechanistic understanding of multistage radiation carcinogenesis will be improved using modelling for improved risk assessment. Quantitative biophysical models will be developed for crucial steps in the process, which will result in a more reliable and accurate quantification of the health effects of radiation at low doses.

RISC-RAD is designed to be a flexible Integrated Project: 20% of the budget is reserved for external calls for research (open to organisations not in the project) to develop topics requiring additional effort, such as research on chromatin structure, cell signalling, etc. In addition, further internal calls for research dedicated to existing RISC-RAD partners will be made as the project progresses, and could include studies on cancer development in mouse models, state-of-the-art reviews, and efforts to improve interdisciplinary collaboration. Training activities will cover specialised courses open to both RISC-RAD partners and other third parties, and funds for short-term mobility for researchers within the partnership.

Identification of genetic factors, mechanisms of tumourigenesis

Quantification of risk at low and protracted doses of ionising radiation requires the identification of new parameters taking into account the ‘inter-individual’ differences in radiation responses. The leading research teams in RISC-RAD will join forces to study ionising radiation-induced DNA damage response/repair epigenetic effects and genomic instability, mechanisms/genetics and modelling of multistage radiation tumourigenesis. The project will improve understanding of the various steps involved in the process of radiation-induced tumourigenesis. It aims to answer a number of important questions including: Who is at higher risk? What are the quantifiable risks of low and protracted doses? What are the mechanisms through which risk factors act? When and how do factors modifying risk exert their influence? Is there a link between individual high dose (short-term) and low dose (long-term) radio-sensitivity?

The project will stress that the identification of genetic factors in the processing of radiation-induced DNA damage is vital for the re-evaluation of current radiation protection measures and the development of future standards.

Improved public radiation protection, new insights on cancer

Nuclear power has an excellent overall health and safety record in Western Europe. Radiation protection has always been a significant part of nuclear research and the understanding derived from these studies underlies the health and safety standards and exposure limits established today. However, understanding of the effects of low and protracted doses of ionising radiation is considerably less than those caused by high intensity, short-term exposures.

The RISC-RAD results will improve understanding of the effects of low and protracted exposure to ionising radiation and enable improved and more appropriate standards to be established. This will enhance public health and safety particularly in populations exposed to higher-than-average natural or background radiation. The fundamental research will also improve the general understanding of the genesis of cancerous cells, especially the mechanisms involved in the interaction of ionizing particles with cells and genetic material and the subsequent processes that turn a healthy normal cell into a cancer tumour.

Project website:
http://www.riscrad.org

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