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

Abstract

This study examined alpha (α-) particle radiation effects on global changes in gene expression for the purposes of identifying potential signaling pathways that may be involved in Radon (222Rn) gas exposure and lung carcinogenesis. Human lung fibroblast cells were exposed to α-particle radiation at a dose range of 0–1.5Gy. 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>|2|) of which 32% were upregulated and 68% downregulated. Fourteen of the high expressing genes (>|4| 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, 24h 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 α-particle induced lung carcinogenesis.