Genetic and epigenetic features in radiation sensitivity

Abstract

Recent progress especially in the field of gene identification and expression has attracted greater attention to the genetic and epigenetic susceptibility to cancer, possibly enhanced by ionising radiation. 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. Although only a small percentage of individuals are "hypersensitive" to radiation effects, all medical specialists using ionising radiation should be aware of the aforementioned progress in medical knowledge. The present paper, the second of two parts, reviews human disorders known or strongly suspected to be associated with hypersensitivity to ionising radiation. The main tests capable of detecting such pathologies in advance are analysed, and ethical issues regarding genetic testing are considered. The implications for radiation protection of possible hypersensitivity to radiation in a part of the population are discussed, and some guidelines for nuclear medicine professionals are proposed.

Typical cell signaling response to ionizing radiation: DNA damage and extranuclear damage

“…There are many types of DNA damage induced by radiation, such as single-strand breaks (SSBs) and doublestrand breaks (DSBs), sugar and base modifications, and DNA-protein cross-links [3] . The damaged DNA can be not only recognized by the sensory proteins, leading to recruitment of DNA repair enzymes, but also generate signals to delay cell cycle progression until the DNA damage is repaired.…”

Identification of up-regulated and down-regulated cis-natural antisense transcripts in the human B lymphoblastic cell line IM-9 after X-ray irradiation

“…) and BAX to control the cell cycle, DNA repair and apoptosis (3)(4)(5). As a non-DNA injury phenomena, cell membrane disorder and lipid peroxidation have been observed, which induce activation of signal transduction pathways, such as those with protein kinase C (PKC), c-Jun NH 2 -terminal kinase (JNK), ceramide and/or mitogen-activated protein kinase (MAPK) (3).…”

“…As a non-DNA injury phenomena, cell membrane disorder and lipid peroxidation have been observed, which induce activation of signal transduction pathways, such as those with protein kinase C (PKC), c-Jun NH 2 -terminal kinase (JNK), ceramide and/or mitogen-activated protein kinase (MAPK) (3). Recent studies have revealed that IR generates reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cells, which leads to DNA injury at random sites as well as the non-DNA injury phenomena (3,6).…”

“…2 Notch homolog 1, translocation-associated (Drosophila) (NOTCH1) 2.08 NM002218. 3 Inter-α (globulin) inhibitor H4 (plasma Kallikrein-sensitive glycoprotein) (ITIH4) 2.08 NM001004059.1 Olfactory receptor, family 4, subfamily S, member 2 (OR4S2) 2.07 NM014172. 2 Phosphohistidine phosphatase 1 (PHPT1) 2.06 NR002765.1 DDEF1 intronic transcript 1 (DDEF1IT1) on chromosome 8 2.03…”

Alternative Medicine Techniques Have Non-Linear Effects on Radiation Response and Can Alter the Expression of Radiation Induced Bystander Effects

“…This situation of apparently contradictory findings is also characteristic of the low dose radiation field (Nguyen Alternative medicine techniques alter radiation response and Wu, 2011;Kondo, 2011;Nomura, 2011;Zyuzikov, et al 2011). In the latter field however it is now clear that different cell lines, different radiation exposures and even media composition give different results (Bourguignon et al 2005;Ponnaiya et al 1997, Morgan andSowa, 2009;Little, 2010;Dainiak, 2011). This could suggest that these very subtle and sensitive responses are of little relevance in risk assessment.…”