Ionizing Radiation-Induced DNA Damage, Response, and Repair

Abstract

By utilizing the strategies outlined above, it may be possible to exploit differences between tumor and somatic cell DRR pathways, specifically their DSB repair mechanisms, to improve the therapeutic ratio of IR.

A Pooled Mutational Analysis Identifies Ionizing Radiation-Associated Mutational Signatures Conserved Between Mouse and Human Malignancies

“…Ionizing radiation interacts directly with DNA, producing double-strand breaks, but also produces chemical changes in DNA through the production of water-derived free radicals also known as reactive oxygen species 13 . As secondary events, reactive oxygen species interact with DNA through a variety of mechanisms, producing base damage, crosslinking and single strand breaks [13][14][15] .…”

“…As secondary events, reactive oxygen species interact with DNA through a variety of mechanisms, producing base damage, crosslinking and single strand breaks [13][14][15] . The relative diversity of free radicals and molecular interactions induced by IR may help to explain the complexity of IR-associated mutational signatures, why multiple signatures are present in IR-induced malignancies, and why some of these signatures may be present in malignancies produced by other non-IR mutagens.…”

The Ketogenic Diet as an Adjuvant Therapy for Brain Tumors and Other Cancers

“…Whether the KD and/or caloric restriction reduces the formation of RNS is as yet unknown. In fact, the main effect of the KD or CR may not be in altering the amount of radiation-induced damage, but may in fact be in modulating the ability of tumor and normal cells to repair radiation-induced damage (Klement and Champ 2014;Santivasi and Xia 2014). Studies have shown that caloric restriction can enhance DNA repair in normal cells (Heydari et al 2007); however, this may not be the case in tumor cells, and the differential response of tumor cells and normal cells to genotoxic stress may be mediated by reduced IGF1 and glucose in the tumor cells.…”

End-processing nucleases and phosphodiesterases: An elite supporting cast for the non-homologous end joining pathway of DNA double-strand break repair

“…They are also induced by exogenous DNA damaging agents such as ionizing radiation [4], radiomimetic drugs [5], and oxidative stress [6]. The repair of these lesions is essential in order to maintain cellular homeostasis and genomic integrity, and a failure to do so causes chromosome loss or rearrangements contributing toward tumorigenesis and cell death.…”