DNA Damage Radiosensitizers Geared Towards Hydrated Electrons

Hypoxia, a hallmark of solid tumors, which account for ca. 80% of cancer cases, makes the cancer cells resistant toward ionizing radiation and as a consequence to radiotherapy, one of the most common modality employed against tumor. Oxygen present in significant amounts in the normoxic cells fixes DNA damage exerted by the radiation-formed hydroxyl radicals which leads to about three folds larger radiosensitivity of the normoxic cells compared to the hypoxic ones. The imparted reactivity of hydroxyl radicals (•OH) in the absence of oxygen and presence of equimolar to the •OH radicals number of solvated electrons under these conditions (under normoxia hydrated electrons (ehyd) react with the dissolved oxygen leading to relatively nonreactive O2•– radicals) suggest the necessity of the employment of sensitizers sensitive to the hydrated electrons for an efficient radiotherapy. In the present chapter several groups of radiosensitizers geared towards hydrated electrons are thoroughly discussed. In Introduction we show how the hypoxic conditions influence cellular damage induced by ionizing radiation. Then we demonstrate that hydrated electrons do not have significant DNA damaging potential although they effectively bind to DNA (due to the subsequent protonation of the anions formed in result of electron attachment to DNA). Finally, we will draw the readers’ attention to the need for using radiosensitizers reacting with hydrated electrons along with ionizing radiation. Introduction is followed by three sections devoted to the discussed classes of radiosensitizers (1) modified nucleosides, (2) oxygen mimetics and (3) metallic nanoparticles and metal complexes. Lastly, the review is concluded with a short summary, where the advantages and disadvantages of all the discussed classes of sensitizers are compiled.