title: 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.
authors.affiliation: Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Sciences Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India.
authors.forename: Sneh M
authors.initials: SM
authors.lastname: Toprani
authors.affiliation: Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Sciences Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India biraj@barc.gov.in birajalaxmi@yahoo.co.in.
authors.forename: Birajalaxmi
authors.initials: B
authors.lastname: Das
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D020552:Comet Assay; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D005720:Gamma Rays; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects*; D008297:Male; D015854:Up-Regulation
chemical_list: D004247:DNA; D045643:DNA Repair Enzymes