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Assessment of Radiation Effects by Molecular and Cellular Approaches

Genetics Unit Westlakes Research Institute Westlakes Science and Technology Park Moor Row, Cumbria CA24 3JZ United Kingdom

In September 1994 physicians and scientists previously separated by political systems in Europe met in Ulm, Germany, to discuss and share their knowledge on the biological and health consequences of human exposure to radiation. The workshop was sponsored by a grant from the International Searle-Foundation for Medical Prevention and Epidemiology and specifically addressed the effectiveness and availability of biological markers for both assessing the extent of radiation exposure and predicting cancer and other health outcomes. It is generally recognised that the deleterious effects of radiation arise mainly from the results of initial lesions induced in deoxyribonuleic acid, DNA. The consequences of this damage to the genetic material can be considered at different levels of biological organisation ranging from the cell to the specific tissue and ultimately to clinical end points. The extent to which these biological responses can be incorporated into a protocol for the examination of radiation exposed persons is a central theme in these workshop proceedings.

One session was devoted to familiarisation with scenarios of radiation exposures of large numbers of people and covered both health effects and biological marker studies. Although concentrating on incidents in the former Soviet Union, an update of the Japanese A bomb data was included. The workshop then examined the molecular approaches for studying cellular characteristics and responses which underly the integrity of cell systems and their ability to respond to radiation-induced lesions. Radiation cytogenetics was comprehensively reviewed with the recognition that the primary biomarker routinely used for assessing the extent of ionising radiation exposure is chromosome aberration frequency. It was acknowledged that advances in fluorescence in situ hybridisation, which enable stable chromosome aberrations to be identified, are beginning to realise their potential for the evaluation of chronic and historical exposures. Other methods for measuring DNA damage such as mutation assays, single cell gel electrophoresis, micronucleus frequency, offer the advantages of quicker and automated analysis but still require validation. Such studies are aimed at measuring the extent of exposure, and it was the hope and anticipation of this workshop that the current advances spearheaded by the Human Genome Project would extend this approach and also lead to more specific markers of effect and health outcome. The late pathological consequences attributable to high doses of radiation, e.g. skin changes, haemopoietic effects, were also considered, including the respiratory effects resulting from inhalation of radionuclides. The possibility of screening the late carcinogenic effects by using specific markers of oncogenesis, together with the realisation that individuals differ in their response to radiation, led to discussions on the development of new concepts of risk assessment based on individual responses. Such an approach could lead to the provision of individually tailored therapeutic regimes aimed at preventing or reducing the possibility of the occurrence of late effects. In addition, it was suggested that neither standard epidemiological approaches using human data nor lifetime animal studies will provide the information for establishing low dose risks. The possibility of biological markers linking exposure and effect will, however, provide the mechanistic understanding which is needed to establish the lower end of dose-response relationships.

The proceedings comprise a comprehensive and formidable review of advances being made in the assessment of radiation-induced biological damage and should provide an invaluable update to those active in radiobiology and radiation medicine research. For those working in operational radiological protection and risk assessment the technical depth might seem daunting, but this volume provides a good opportunity to see how current biological advances are influencing thinking on exposure monitoring and ill health prediction.

Footnotes

Edited by T.M. Fliedner, E.P. Cronkite and V.P. Bond AlphaMed Press, 1995. Dayton, Ohio $69 (iii + 347 pp., illustrated) ISSN 1066-5099

Reprinted with permission from Radiation Protection Dosimetry, Vol. 63, No. 1, 1996, Nuclear Technology Publishing, Ashford, Kent, United Kingdom.

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