γ-radiation induced chromosomal aberrations and alteration of gene expression in human peripheral blood lymphocyte show good correlation: implications in molecular biodosimetry

Humans are at risk of exposure to ionizing radiation due to professional, diagnostic and therapeutic exposures. In addition, large scale exposures triggered either accidentally or by natural calamities or due to perceived terrorist threats are also possible. The median lethal dose of radiation (LD_50/60, without medical intervention) for humans is quite low and is estimated to be 4.5 Gy. Due to this, it is imperative that biological dosimetry is conducted on all exposed or suspected-to-be exposed human population in shortest possible time for triage and appropriate medical intervention to save precious human lives. The 'gold standard' of contemporary biological dosimetry is dicentric assay (DCA) wherein dicentrics on chromosomes of human peripheral blood lymphocytes (HPBL) exposed to radiation is measured. At the present time it is considered as the reliable biomarkers of radiation exposure. However, DCA suffers from methodological limitation making applications of the technique practically impossible for a large number of samples in short time. In order to overcome this limitation of DCA, it is important to look for molecular biomarker of radiation exposure. In this study, it is our endeavor, to identify genes which correlate with radiation exposure to develop a reliable and sensitive molecular biodosimeter. Fresh human blood was exposed to 0.5, 1 and 2 of γ-rays (5.5 Gy min^-1) and immediately subjected to DCA as well as DNA Microarray (Affymetrix Platform) and quantitative real-time PCR (qPCR). DNA Microarray revealed 20 early radiation response genes (RRGs) in HPBL exposed to γ-rays. Out of these, 8 genes, which showed dose response relationships, have been validated by qPCR at 0 and 24 h post-irradiation incubation periods using GAPDH and 18 S genes as normalizers. Simultaneous linear regression analysis of dose dependent DCA was performed for each gene, which exhibited good correlation. We do, however, see influence of inter-individual variability in the data. The presentation shall dwell on these issues and their implications on molecular biodosimetry. (author)