Title: Radiation-induced genomic instability: manifestations and mechanisms

Authors: E.G. Wright

Addresses: University of Dundee, Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK

Abstract: There is considerable evidence that delayed death, gene mutations and a variety of chromosomal abnormalities can be demonstrated in cells that are not themselves irradiated but are the progeny of cells exposed to ionising radiation many cell divisions previously. These effects are collectively referred to as radiation-induced genomic instability. At present, we have limited understanding of the underlying mechanism(s) and there are differences in the expression of instability between different cell types and a strong dependence on genetic factors (||genetic predisposition||). In all studies where delayed effects of radiation have been demonstrated they have been demonstrated reproducibly at frequencies considerably greater than conventional mutation frequencies arguing against instability being due to ||conventional|| mutational mechanisms Current understanding favours epigenetic mechanisms and free radical-mediated processes have been suggested. Such processes could explain the data demonstrating that cells can develop genomic instability by an indirect inter-cellular (||bystander||) mechanism. Radiation-induced bystander effects result in unirradiated cells exhibiting responses that are typically associated with radiation exposure as a consequence of contact with irradiated cells or receiving soluble signals from irradiated cells. Bystander effects and instabilities may all reflect inter-related aspects of non-targeted non-specific inflammatory-type responses to radiation-induced stress and injury.

Keywords: genomic instability; bystander effects; clastogenic factors; oxidative stress; radiogenic malignancy; radiation risk.

DOI: 10.1504/IJLR.2004.003875

International Journal of Low Radiation, 2004 Vol.1 No.2, pp.231 - 241

Published online: 10 May 2004 *

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