Inter-individual Differences in Radiosensitivity based on CDKN1A, GADD45A, DDB2, BCL2 and TRX Gene Expression in Human Lymphocytes

Abstract

Transcriptomic signatures of radioresponsive genes are recently explored as a powerful tool for biodosimetry. As cytogenetics remains the gold standard and a robust approach for wide-scale testing during radiologic emergencies, the utility of molecular signatures remains to be adequately validated. The present study analyzed the expression profiles of five highly responsive genes to radiation: B-cell lymphoma 2 (BCL2), DNA damage-binding protein 2 (DDB2), cyclin-dependent kinase inhibitor 1A (CDKN1A), growth arrest and DNA-damage-inducible alpha (GADD45A) and thioredoxin (TRX). Ex vivo exposure of peripheral blood lymphocytes from 17 healthy subjects, aged 21 to 53 years, at 2 Gy radiation appeared to mobilize the index genes involved in cell cycle arrest (GADD45A and CDKN1A) and the binding to DNA lesion to facilitate excision repair (DDB2). However, the transcription of pro-survival protein BCL2 and redox repair antioxidant protein TRX were not as reliable as molecular biodosimeters considering the variability among individual responses. Nevertheless, the significant correlations observed among the genes emphasize their synchronized roles during DNA damage and redox response. Gender-based differences in gene expression were not detected. These findings indicated the diverse transcriptional regulation of p53-dependent pathways in radiation-exposed lymphocytes. Further validation in more patients during healthy and diseased states could contribute to the clinical application of gene-based radiation biodosimetry.