Genetic and epigenetic features in radiation sensitivity

Abstract

Recent progress especially in the field of gene identification and expression has attracted greater attention to genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. It has been proposed that the occurrence and severity of the adverse reactions to radiation therapy are also influenced by such genetic susceptibility. This issue is especially important for radiation therapists since hypersensitive patients may suffer from adverse effects in normal tissues following standard radiation therapy, while normally sensitive patients could receive higher doses of radiation offering a better likelihood of cure for malignant tumours. This paper, the first of two parts, reviews the main mechanisms involved in cell response to ionising radiation. DNA repair machinery and cell signalling pathways are considered and their role in radiosensitivity is analysed. The implication of non-targeted and delayed effects in radiosensitivity is also discussed.

A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas

“…Radiation has potential DNA damaging and carcinogenic effects, and causes single- and double-strand breaks. Double-strand breaks are thought to be particularly important for cancer development, and represent the major effect of β -radiation, for example, 131 I, although the radiation effects are complex and numerous (Bourguignon et al , 2005; Harper and Elledge, 2007; Riley et al , 2008). However, DNA damage is repaired within the few hours or days after radiation exposure, and our signature would then reflect the long-lasting consequences of incorrectly repaired DNA damage.…”

Twilight effects of low doses of ionizing radiation on cellular systems: a bird’s eye view on current concepts and research

“…Bystander cells manifest a multitude of biological consequences, such as genetic and epigenetic changes, alterations in gene expression, activation of signal transduction pathways and delayed effects in their progeny. It is generally acknowledged that these responses result upon the levels of the secreted factors and the possibility of fixing the DNA damages and the type of cells that receive the signals [128,129].…”

Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer research

“…Radiosensitivity is often observed in patients with genetic disorders associated with a defect in the DNA damage response and cell death pathways (reviewed in [101; 102; 103]. Among these are such well characterized syndromes as AT, AT-like disorder, Nijmegen breakage syndrome (NBS), Fanconi anemia (FA), Ligase IV syndrome, Seckel syndrome, Li-Fraumeni syndrome and familial retinoblastoma.…”