Effects of alpha particle radiation on gene expression in human pulmonary epithelial cells

The general public receives approximately half of its exposure to natural radiation through alpha (α)-particles from radon (222Rn) gas and its decay progeny. Epidemiological studies have found a positive correlation between exposure to 222Rn and lung carcinogenesis. An understanding of the transcriptional responses involved in these effects remains limited. In this study, genomic technology was employed to mine for subtle changes in gene expression that may be representative of an altered physiological state. Human lung epithelial cells were exposed to 0, 0.03, 0.3 and 0.9 Gy of α-particle radiation. Microarray analysis was employed to determine transcript expression levels 4 h and 24 h after exposure. A total of 590 genes were shown to be differentially expressed in the α-particle radiated samples (false discovery rate (FDR) ≤ 0.05). Sub-set of these transcripts were time-responsive, dose-responsive and both time- and dose-responsive. Pathway analysis showed functions related to cell cycle arrest, and DNA replication, recombination and repair (FDR ≤ 0.05). The canonical pathways associated with these genes were in relation to pyrimidine metabolism, G2/M damage checkpoint regulation and p53 signaling (FDR ≤ 0.05). Overall, this gene expression profile suggests that α-particle radiation inhibits DNA synthesis and subsequent mitosis, and causes cell cycle arrest.