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The physico-chemical basis of DNA radiosensitization: Implications for cancer radiation therapy
(2018)
High-energy radiation is used in combination with radiosensitizing therapeutics to treat cancer. The most common radiosensitizers are halogenatednucleo-sides and cisplatin derivatives, and recently also metal nanoparticles have been suggested as potentialradiosensitizing agents. The radiosensitizingaction of these compounds can at least partly be ascribed to an enhancedreactivity towards secondary low-energy electrons generated along the radiation track of the high-energyprimary radiation, or to an additional emission of secondary reactive electrons close to the tumor tissue. This is referred to as physico-chem ical radiosensitization. In this Conceptarticle we presentcurrent experimental methodsused to study fundamentalprocesses of physico-chemical radiosensitization and discuss the most relevant classes of radiosensitizers. Open questions in the current discussions are identified and future directions outlined, which can lead to optimized treatment protocols or even novel therapeuticconcepts.
2-Amino-2-(hydroxymethyl)-1,3-propanediol (TRIS) and ethylene-diaminetetraacetic acid (EDTA) are key components of biological buffers and are frequently used as DNA stabilizers in irradiation studies. Such surface or liquid phase studies are done with the aim to understand the fundamental mechanisms of DNA radiation damage and to improve cancer radiotherapy. When ionizing radiation is used, abundant secondary electrons are formed during the irradiation process, which are able to attach to the molecular compounds present on the surface. In the present study we experimentally investigate low energy electron attachment to TRIS and methyliminodiacetic acid (MIDA), an analogue of EDTA, supported by quantum chemical calculations. The most prominent dissociation channel for TRIS is through hydroperoxyl radical formation, whereas the dissociation of MIDA results in the formation of formic and acetic acid. These compounds are well-known to cause DNA modifications, like strand breaks. The present results indicate that buffer compounds may not have an exclusive protecting effect on DNA as suggested previously.