title: Effects of alpha particle radiation on gene expression in human pulmonary epithelial cells.
abstract: The general public receives approximately half of its exposure to natural radiation through alpha (α)-particles from radon ((222)Rn) gas and its decay progeny. Epidemiological studies have found a positive correlation between exposure to (222)Rn 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 0.9Gy of α-particle radiation. Microarray analysis was employed to determine transcript expression levels 4h and 24h 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.
authors.affiliation: Environmental and Radiation Health Sciences Directorate, Health Canada, Ottawa, Ontario, Canada K1A 0K9. Vinita Chauhan@hc-sc.gc.ca
authors.forename: Vinita
authors.initials: V
authors.lastname: Chauhan
authors.forename: Matthew
authors.initials: M
authors.lastname: Howland
authors.forename: Amy
authors.initials: A
authors.lastname: Mendenhall
authors.forename: Shifawn
authors.initials: S
authors.lastname: O'Hara
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Stocki
authors.forename: James P
authors.initials: JP
authors.lastname: McNamee
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Wilkins
mesh_terms: D000512:Alpha Particles; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism / Q000528:radiation effects*; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000166:cytology