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Report

Targeted and non-targeted  effects of ionising radiation:
Implications for low  dose risk

Worshop - Report

Peter O'Neill


MRC Radiation & Genome Stability Unit, Harwell, UK

 

The 2nd workshop of the EC funded concerted action, NET-EULEP (contract co-ordinator Professor J. Hopewell, Churchill Hospital Research Institute, Oxford, UK) was organised by Working Party 2. The scientific area of research covered by Working Party 2 is on 'Radiation response and low dose risk'. The Workshop was held at the PBH-Physikzentrum, Bad Honnef, Germany from 10-12 July 2002. 49 participants attended the workshop, representing scientists from the various EC cost shared actions and other invitees including members from Working Party 1 and scientists from non-EC funded projects. Eight young scientists also attended the workshop to enhance their understanding/training in the field and to encourage future career development in this field of research.

The objectives of the Workshop were:

  1. to provide a forum for the scientists, undertaking research within the various EU consortia and non-EU supported research relating on the topic of the Workshop, to exchange ideas, information and views and discuss its input into the 'Implications for low dose risk',
  2. To provide synergism and gain 'added value' between the research programmes funded by the EU and foster interactions and exchange of ideas between the programmes,
  3. To disseminate to a wider audience the research undertaken in EC funded programmes through publication of a Workshop report.

The Workshop programme was organised into 6 sessions: ● The role of ionising radiation in the promotion of cancer ● Radiation-induced genome instability and bystander effects: relevance to cancer ● Radiation-induced chromosomal aberrations and telomere damage: cause or consequence of cancer induction ● DNA: radiation target for induction of carcinogenesis ● Threshold at low dose radiation in cancer induction-targeted and non-targeted effects- requirement for modellers ● Genetic Pre-disposition to ionising radiation.

Most of the sessions had two main speakers to give a balanced view to the topic under discussion. All participants were encouraged to contribute to the discussions, which were generally lively and very constructive. Two teaching lectures were presented on 'Radiation-induced DNA repair' and 'Mammography: radiological risk?'. During the NET-EULEP workshop, we had the pleasure of devoting a session to the Friedrich Dessauer

Prize. The recipient of the Friedrich Dessauer Award 2002 was Prof. Dr. Markus Löbrich (Homburg, Germany) and Prof. Dr. Dr. h.c. Christian Streffer (Essen, Germany) delivered the Friedrich Dessauer Lecture 2002.

The main scientific outcomes and questions arising.

The presentations represented a mix, focussing on targeted and non-targeted effects, e.g. genetic instability and bystander effects, of radiation. Following the discussions from the 1st Workshop considerable discussion focussed on what is the cellular target for radiation-induced non-targeted effects and what is the relative contribution of targeted and non-targeted effects to carcinogenesis. This new paradigm, which may need to be considered when developing models of radiation effects at the cellular and organ level, requires the development of molecular mechanism(s) to address many of the questioned posed relating to dose rate, dose and cell type. The question of synergism between endogenous DNA damage and that induced by radiation as contributing to low LET radiation effects was also addressed and may also provide insights into non-targeted effects. Many of the sessions brought together expertise on chromatin structure, DNA/chromosomal damage and repair and cell cycle effects on identification of the critical features of radiation-induced DNA damage/processing which may lead to chromosome aberrations and mutations. DNA DSB were mainly discussed in terms of their repair and identifying the various pathways involved. These findings posed interesting questions concerning the role of NHEJ and HR in the maintenance of genome stability following radiation and that HR is important in cell proliferation and radiosensitivity. Telomere maintenance involves NHEJ proteins and may be related to radiation response of cells. A question that arose was the link between telomere maintenance and radiation carcinogenesis. Evidence was presented indicating that a single electron track may cause chromosome aberration through lesion-non lesion interaction. The contribution of non-DSB clustered DNA damage and its processing needs to be considered in the biological response at low doses. The question as to whether radiation has a promotional effect on cancer induction remains open, although risk-related radiation effects on cell proliferation at the organ level cannot be excluded.

Improvements in the models of radiation effects at the cellular/tissue level for extrapolation to low dose, low dose rate may best arise from active interactions between modellers and experimentalists. With respect to radiation protection, the question was posed by the modellers as to whether the bystander effect influences risk factors. . It is therefore imperative to ascertain the relevant contributions of targeted and non-targeted effects to the assessment of risk factors of ionising radiation.

The Workshop conclusions:

  1. The Workshop brought together researchers from EU and non-EU funded projects to gain added value and exchange information.
  2. The outcome of the workshop was very positive providing a platform for interactions and exchange of information/ideas between the various aspects of radiation research being undertaken under the topic of 'Radiation response and low dose risk'. The two-way exchange of the ideas between the experimentalists and the modellers is positive as many of the experiments are conducted at doses high relative to environmental risks due to the sensitivity of detection of the various techniques. The workshop contributed to transmission of information between the EU funded programmes, heightened awareness of the different aspects of the research and identified potential areas of added value, such as a) the relative contribution of targeted and non-targeted effects to the assessment of risk factors of ionising radiation and b) identification of the critical features of radiation damage in cells leading to mutations, chromosomal aberrations, telomere shortening, cell proliferation etc. The sessions focussed on topics relevant to low dose risk assessment and identified areas where more research is required and ask important questions of relevance to carcinogenesis.
  3. Interactions between the programmes are to be encouraged to foster synergism between the various research approaches and enhance inter-disciplinary interactions to understand and address the questions posed by the different disciplines.
  4. The report of the Workshop will be published on the WEB in the Newsletter of EULEP.


Encourage young scientists to attend to contribute to their training in the field of radiation research and allied fields.                                                                                                                                                                                   

 


For further information

Peter O'Neill
DNA Damage Group.
 MRC Radiation & Genome stability unit,
Harwell, Didcot,
Oxon, OX11 0RD, UK

e-mail: p.oneill@har.mrc.ac.uk