Role of base excision repair genes and proteins in gamma-irradiated resting human peripheral blood mononuclear cells.

ABSTRACT

Ionising radiation induces several isolated and clustered DNA lesions in human cells. Depending on the type of lesions, DNA repair pathways get activated to maintain the integrity of the genome. Base excision repair (BER) pathway is known to repair single-strand breaks and base damages through short- and long-patch genes and proteins. In the present study, attempt has been made to study the role of BER genes and proteins in resting human peripheral blood mononuclear cells (PBMCs) exposed to gamma radiation. Venous blood samples were collected from 20 random and healthy individuals with written informed consent. Dose-response and time-dependent changes at the level of DNA damage, transcription and protein expression were studied in PBMC. Dose-response studies were done in PBMC exposed between 0.1 and 2.0 Gy, whereas time-dependent changes in post-irradiated PBMC were studied up to 240 min. Our results have shown a significant (P ≤ 0.05) dose-dependent increase in the percentage of DNA in tail (%T) among the individuals studied. At transcriptional level, LIGASE3, MBD4 and LIGASE1 showed significant up-regulation (P ≤ 0.05) at 4h compared to 0h. Short-patch BER proteins such as OGG1 and LIGASE3 showed significant increase (P ≤ 0.05) in expression at lower doses (<0.6 Gy), whereas long-patch BER proteins such as MBD4, FEN1 and LIGASE1 showed an increase in expression at higher doses (1.0 and 2.0 Gy), suggesting dose-dependent and pathway-specific role of BER proteins in human PBMCs at G0/G1. In conclusion, BER genes and proteins play an active role in repairing radiation-induced DNA damage in resting PBMC, which has important biological significance in terms of DNA repair process in humans.