The importance of radiation chemistry to radiation and free radical biology (The 2008 Silvanus Thompson Memorial Lecture).
Biological effects of radiation are manifest over timescales extending to years. However, many chemical events are complete in milliseconds; after this time, adding oxygen to irradiated hypoxic cells no longer enhances radiosensitivity. This does not mean that damage pathways cannot be modified; the potential gain from chemical modulation of early events is as large as any associated with later pathways, and the prognostic importance of variations in levels of small molecules active in fast free radical pathways is as important as any associated with genetic make-up. Reactive oxygen species are much invoked in the wider context, but are frequently undefined and seldom measured unambiguously. Radiation chemistry has much to offer to both radiation and free radical biology. An appreciation of the interlinked parameters of time, spatial distribution and yield is well developed, as are methods to generate specific radicals in known concentrations and to monitor their reactions directly. Intense clinical interest in the 1980s in hypoxic cell radiosensitizers, developed from radiation chemical studies, has waned, but the goal of eliminating hypoxic radioresistance remains attractive. Nitric oxide may be more important than oxygen in determining hypoxic radiosensitivity, and radiation chemistry provides the tools to understand the mechanisms and the limitations of in vitro models. Imaging hypoxia in tumours relies heavily on free radical chemistry and radiolysis methods to understand the mechanistic basis for diagnostic agents. Quantitation of the chemical reactivity of free radicals is a cornerstone of radiation chemistry via the language, concepts and mathematics of chemical kinetics, which are equally applicable to understanding the molecular pathways in radiobiology.
Wardman
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P
University of Oxford, Gray Cancer Institute, Mount Vernon Hospital, Northwood, Middlesex, UK. peter.wardman@rob.ox.ac.uk
D016477:Artifacts; D005456:Fluorescent Dyes; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology; D015538:Nitrosation; D018384:Oxidative Stress; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D011853:Radiobiology / Q000379:methods*; D011854:Radiochemistry / Q000379:methods*; D017382:Reactive Oxygen Species / Q000378:metabolism
D005456:Fluorescent Dyes; D005609:Free Radicals; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide