Gene expression responses in human lung fibroblasts exposed to alpha particle radiation

This study examined alpha (alpha-) particle radiation effects on global changes in gene expression for the purposes of identifying potential signaling pathways that may be involved in Radon (Rn-222) gas exposure and lung carcinogenesis. Human lung fibroblast cells were exposed to alpha-particle radiation at a dose range of 0-1.5 Gy. Twenty-four hours post-exposure, transcript modulations were monitored using microarray technology. A total of 208 genes were shown to be dose-responsive (FDR adjusted p < 0.05, Fold change > vertical bar 2 vertical bar) of which 32% were upregulated and 68% downregulated. Fourteen of the high expressing genes (> vertical bar 4 vertical bar fold) were further validated using alternate technology and among these genes, GDF15 and FGF2 were assessed at the protein level. GDF15, a known marker of lung injury, had expression levels 3-fold higher in exposed cell culture media, 24 h post-irradiation as detected by ELISA. Further, pathway analysis of the dose-responsive transcripts showed them to be involved in biological processes related to cell cycle control/mitosis, chromosome instability and cell differentiation. This panel of genes with particular focus on GDF15 may merit further analysis to determine their specific role in mechanisms leading to alpha-particle induced lung carcinogenesis. Crown Copyright (C) 2014 Published by Elsevier Ltd. All rights reserved.