Radio-adaptive response of base excision repair genes and proteins in human peripheral blood mononuclear cells exposed to gamma radiation

Abstract

Radio-adaptive response is a mechanism whereby a low-dose exposure (priming dose) induces resistance to a higher dose (challenging dose) thus significantly reducing its detrimental effects. Radiation-induced DNA damage gets repaired through various DNA repair pathways in human cells depending upon the type of lesion. The base excision repair (BER) pathway repairs radiation-induced base damage, abasic sites and single-strand breaks in cellular DNA. In the present study, an attempt has been made to investigate the involvement of BER genes and proteins in the radio-adaptive response in human resting peripheral blood mononuclear cells (PBMC). Venous blood samples were collected from 20 randomly selected healthy male individuals with written informed consent. PBMC were isolated and irradiated at a priming dose of 0.1 Gy followed 4h later with a challenging dose of 2.0 Gy (primed cells). Quantitation of DNA damage was done using the alkaline comet assay immediately and expression profile of BER genes and proteins were studied 30 min after the challenging dose using real-time quantitative polymerase chain reaction and western blot, respectively. The overall result showed significant (P ≤ 0.05) reduction of DNA damage in terms of percentage of DNA in tail (%T) with a priming dose of 0.1 Gy followed by a challenging dose of 2.0 Gy after 4 h. Twelve individuals showed significant (P ≤ 0.05) reduction in %T whereas eight individuals showed marginal reduction in DNA damage that was not statistically significant. However, at the transcriptional level, BER genes such as APE1, FEN1 and LIGASE1 showed significant (P ≤ 0.05) up-regulation in both groups. Significant (P ≤ 0.05) up-regulation was also observed at the protein level for OGG1, APE1, MBD4, FEN1 and LIGASE1 in primed cells. Up-regulation of some BER genes and proteins such as APE1, FEN1 and LIGASE1 in primed cells of resting PBMC is suggestive of active involvement of the BER pathway in radio-adaptive response.

Assessment of Individual Radiosensitivity in Inhabitants of Takandeang Village － A High Background Radiation Area in Indonesia

“…However, it is well known that RAR could be induced by chronic low dose exposure, even though the molecular mechanism underlying RAR is not yet clearly understood. It is assumed that RAR may be either due to the enhanced repair of DNA damage or due to protection against the adverse effects induced by high challenging doses [39]. The high level of DNA damage in people living in HBRAs could come from the high level of reactive oxygen species (ROS).…”

Global Gene Expression Alterations as a Crucial Constituent of Human Cell Response to Low Doses of Ionizing Radiation Exposure

“…IR-induced DNA damage is known to be repaired through various DNA repair pathways depending upon the type of lesion in human cells. Recently, several studies have been carried out to investigate the involvement of both non-homologous end joining (NHEJ) and base excision repair (BER) genes and proteins in human PBMC under RAR settings [ 57 , 58 ]. BER pathway repairs IR-induced single-strand breaks, base damage, and abasic sites in both nuclear and mitochondrial DNA whereas NHEJ is involved in fixing DNA double stranded breaks (DSBs) in human cells.…”

“…The expression profiles of BER and NHEJ genes and proteins were examined 30 min and up to four hours after the challenging dose using qRT-PCR reaction and western blotting, respectively. BER genes such as APE1 , FEN1 and LIG1 showed significant up-regulation at mRNA level as well as at the protein level for APE1, MBD4, OGG1, FEN1 and LIG1 in primed cells [ 58 ]. NHEJ genes XRCC5 , XRCC6 , NHEJ1 and LIG4 were statistically significantly overexpressed at four hours post-irradiation both at the transcript and protein levels [ 57 ].…”

Dose and Radioadaptive Response Analysis of Micronucleus Induction in Mouse Bone Marrow

“…Radio-adaptive responses are a type of NTE manifested as a decrease in either acute detrimental radiation-induced or spontaneous biological health effects following exposures to low-dose radiation (mostly low-linear energy transfer (LET) radiation quality) [ 5 , 12 , 13 , 14 ]. Radio-adaptation has been reported for a variety of biological endpoints related to cellular toxicity and genotoxicity in vitro [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. In relation to human radiation risk estimates, the most valuable experimental studies are those studying in vivo biological effects.…”