Cellular radiosensitivity: how much better do we understand it?
OBJECTIVE
Ionising radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumourigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H(2)O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies.


CONCLUSIONS
In the past 50 years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation.
Jeggo
Penny
P
Genome Damage and Stability Centre, Science Park Road, University of Sussex, Falmer, Brighton, East Sussex BN1 9RQ, UK. p.a.jeggo@sussex.ac.uk
Lavin
Martin F
MF
D016923:Cell Death / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D005609:Free Radicals / Q000737:chemistry / Q000528:radiation effects*; D011675:Pulse Radiolysis; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects*
D005609:Free Radicals