Effect of dose modifiers on radiation-induced cellular DNA damage
bookPart
In research on the modification by chemical agents of the effects of ionizing radiation, most attention has been directed towards application of radiosensitizing or radioprotective drugs in cancer radiotherapy. Studies on radiosensitization have led to the development of a broad class of compounds which cause pronounced differential radiosensitization of cells under hypoxic conditions but show no activity in oxic cells. Radiobiological studies on the general occurrence of the oxygen effect led to the conclusion that the hypoxity of tumor cells makes them relatively radioresistant. This is a major factor in the failure of radiotherapeutic treatment of some human tumors. The large majority of radiosensitizers established as such are of the oxygen-mimetic type, the activity of which is governed largely by their electron-affinity. Other mechanisms involved in sensitization are changes in intracellular thiol levels, inhibition of cellular DNA repair processes, and/or inhibition of oxygen utilization. The development of radioprotective drugs has shown less progress. In the past, thousands of compounds were synthesized and screened for their protective capacity against damage arising from whole body irradiation, with only limited success. One compound, however, the thiophosphate WR24721, appeared sufficiently promising to warrant further investigation of its potential as a protective agent against destruction of normal tissue during radiotherapy of cancer. In this paper, special attention is given to the influence of oxygen on the induction of radiation damage in DNA of mammalian cells after sensitization by intracellular glutathione depletion. Futhermore, data are presented about the modification of radiation response at the DNA level after in vivo irradiation.
Topics
TNO Identifier
984051
ISBN
978-3-642-75150-9
Source
The Early Effects of Radiation on DNA, pp. 347-362.
Publisher
Springer
Editor(s)
Fielden, E.M.
O’Neill, p.
O’Neill, p.
Pages
347-362
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