The Physico‐Chemical Basis of DNA Radiosensitization: Implications for Cancer Radiation Therapy

Abstract

High-energy radiation is used in combination with radiosensitizing therapeutics to treat cancer. The most common radiosensitizers are halogenated nucleosides and cisplatin derivatives, and recently also metal nanoparticles have been suggested as potential radiosensitizing agents. The radiosensitizing action of these compounds can at least partly be ascribed to an enhanced reactivity towards secondary low-energy electrons generated along the radiation track of the high-energy primary radiation, or to an additional emission of secondary reactive electrons close to the tumor tissue. This is referred to as physico-chemical radiosensitization. In this Concept article we present current experimental methods used to study fundamental processes 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 therapeutic concepts.

Clustered DNA Damages induced by 0.5 to 30 eV Electrons

“…They can cause SSBs, DSBs, crosslinks, and base modifications in DNA [65,66,67], but it is mostly the unrepaired DNA clustered lesions that are responsible for mutagenic, genotoxic, and other potentially lethal effects in the cell. Therefore, finding the cause of such damages could help understand their destructive action in cancer cells and thus contribute to the development of new improved strategies for cancer treatment with radiotherapy and chemoradiation therapy [68,69].…”

Special issue: Dynamics of systems on the nanoscale (2018). Editorial

“…These software packages have been designed to become powerful and universal instruments of computational research in the field of MBN Science, which should play a role of a "virtual microscope" and a "camera" capable to explore, simulate, record and visualize both structure and dynamics of the MBN-world with an atomistic level of accuracy, in order to both reproduce its known features and predict the new ones. In this Topical Issue, many contributions [12][13][14][15][16][17][18][19][20][21][22][24][25][26][27][28][29][30][31][32][33][34][35] provide case studies conducted with these packages and demonstrate their application to a broad variety of topical areas in MBN science as listed at the beginning of this Editorial. To be noted that these universal and powerful software packages are fully applicable to a broad variety of the topical areas of the MBN Science listed above in the introductory part of the Editorial.…”

“…Several studies are concerned with the interaction of radiation with fluorinated molecules, which are used as radiosensitizers in cancer radiation therapy. Among the most widely used therapeutics in the clinics are 5-fluorouracil (5FU) and gemcitabine, which are both highly reactive towards low-energy electrons [29]. Van der Burgt et al [30] have studied the formation of positive ions from 5FU by electron impact from 0-100 eV and by multiphoton ionization using laser thermal desorption.…”

Fragmentation processes of ionized 5-fluorouracil in the gas phase and within clusters

“…5-fluorouracil is a significant chemotherapy drug whose action is primarily associated with inhibiting the synthesis of thymidine and thus DNA replication. Furthermore, it is well established that the substitution of thymine with a 5-halouracil in the genetic sequence of cellular DNA during replication in the presence of these dopants leads to greater sensitivity to ionizing radiation [1][2][3]. In view of the generally rapid replication of cancerous cells compared with healthy cells, this provides a strong basis for the use of halouracil radiosensitizers in radiotherapy.…”