Crosstalk between telomere maintenance and radiation effects: A key player in the process of radiation-induced carcinogenesis

Abstract

It is well established that ionizing radiation induces chromosomal damage, both following direct radiation exposure and via non-targeted (bystander) effects, activating DNA damage repair pathways, of which the proteins are closely linked to telomeric proteins and telomere maintenance. Long-term propagation of this radiation-induced chromosomal damage during cell proliferation results in chromosomal instability. Many studies have shown the link between radiation exposure and radiation-induced changes in oxidative stress and DNA damage repair in both targeted and non-targeted cells. However, the effect of these factors on telomeres, long established as guardians of the genome, still remains to be clarified. In this review, we will focus on what is known about how telomeres are affected by exposure to low- and high-LET ionizing radiation and during proliferation, and will discuss how telomeres may be a key player in the process of radiation-induced carcinogenesis.

Second Gastric Cancer After the Treatment of Primary Stomach Diffuse Large B-Cell Lymphoma

“…For the same dose to an organ RR is less if part of the body is protected [9,11]. When a second primary cancer appears in the irradiated area, it is difficult to confirm its «radio-induced» origin" [18,19]. A tumor is considered as radiation-induced if it is within the irradiated volume with a different histology and is displayed in a period of more than 5 years after irradiation [18,19].…”

Toxicogenetic biomonitoring of occupational risk induced by ionizing radiation

“…The effects of IR involve endogenous signaling events that culminate in oxidative damage to DNA, lipids, proteins and many metabolites, in addition to changes in gene expression, metabolism and epigenetic factors (Reisz et al, 2014). It is well established that IR induce instability in chromosomes and have effects on activation and inactivation of DNA repair mechanisms, induce oxidative damage, but is not yet well established role of IR on telomeric proteins, which are considered to be protective of genome and related to carcinogenesis (Shim et al, 2014). Numerous effects of radiation have been identified in association with mutations and genomic instability (breaks and actions in repair genes), angiogenesis (vascularisation and hypoxia), apoptosis (changes in p53), proliferative signaling (EGCR and TGF-α), suppression of cell cycle (ATM, p53 lock), energy dysregulation (HIF, c-MyC, glycolytic pathways inhibitors), tumor promotion and inflammation (p53 and ROS) and activation and inactivation of metastases (hypoxia, lactate) (Boss et al, 2014).…”

“…High and low doses Shim et al (2014) Mutations and genomic instability. Angiogenesis, apoptosis, proliferation, energy imbalance, inflammation and metastases High and low doses Boss et al (2014) Figure 3.…”

Telomere/telomerase and radiosensitivity

“…Telomeres are the special structures at the ends of chromosome, which are essential for protection against DNA damage signals and ensure genome stability [1] . With the discovery of telomeres and the research in duplication of chromosomes，telomerase is a specialized ribonucleoprotein complex with reverse transcription activity that is minimally composed by the telomerase reverse transcriptase and a RNA template, which is called telomerase RNA component (TERC), for telomere extension during de novo addition of TTAGGG repeats onto chromosome ends.…”