GENOME STABILITY MECHANISMS UNDERLYING RADIATION-INDUCED CHROMOSOMAL ABERRATIONS IN HUMAN CELLS

Abstract

Background: Ionizing radiation is a major source of DNA damage that can cause chromosomal aberrations and compromise genome stability in human cells. Cellular mechanisms that guard against radiation-induced damage to chromosomal integrity such as DNA damage response signaling and repair pathways are required.

Objective:  The objective of this study was to investigate mechanisms of genome stability for radiation-induced chromosomal aberrations in human cells and to evaluate the role of DNA repair pathways in reduction of genomic instability.

Methodology: Human peripheral blood lymphocytes and fibroblast cells were exposed to gamma radiation dose of 0-6 Gy. Cytogenetic analyses including metaphase chromosome assay, micronucleus test and γ-H2AX immunofluorescence were performed to evaluate DNA damage and chromosomal abnormalities. ATM, RAD51 and Ku70 repair proteins were statistically analysed for their expression levels.

Findings: Results showed a dose-dependent increase of chromosomal aberrations. Dicentric chromosomes increased from 1.2% in controls to 31.6% at 6 Gy. γ-H2AX foci as well as DNA repair protein expression increased significantly at moderate doses but decreased at higher exposure levels, indicating that the repair pathways were exhausted.

Conclusions: Mechanisms of genome stability are at work to counteract the radiation-induced chromosomal damage at moderate levels of radiation exposure. Excessive radiation overwhelms the repair mechanisms resulting in persistent genomic instability and chromosomal aberrations.