title: Biological effects of alpha particle radiation exposure on human monocytic cells.
abstract: Radon ((222)Rn) gas produces decay progeny that emits high energy alpha (α)-particles. Epidemiological studies have shown that exposure to (222)Rn is linked with elevated risk of developing lung cancer, however clear mechanisms leading to such effects have not been delineated. Cytokines play a critical role in inflammation and their dysregulated production often contributes to disease pathogenesis. In this study, Bio-plex multiplex technology was employed to investigate modulations of 27 pro-inflammatory cytokines following exposure of human monocytic cells to 1.5 Gy of α-particle radiation. Concurrently, DNA damage was assessed by examining the formation of phosphorylated H2A histone family X (γ-H2AX) sites. Of the 27 cytokines assessed, 4 cytokines were shown to be statistically downregulated by ∼2 fold relative to the untreated controls and included the interleukin (IL) family of proteins (IL-2, IL-15 and IL-17) and macrophage inflammatory protein 1 beta (MIP-1b). Interferon-inducible protein-12 (IP-12), vascular endothelial growth factor and regulated on activation normal T cell expressed and secreted (RANTES) were shown to be high expressors and upregulated. Cells irradiated with α-particles ranging from 0.27 to 2.14 Gy showed statistically significant, dose-dependant increases in γ-H2AX formation. These data suggest that α-particle radiation causes dysregulation in the production of a number of pro-inflammatory cytokines and results in significant DNA damage.
authors.affiliation: Consumer and Clinical Radiation Protection Bureau, Health Canada, ON, 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: Barbara
authors.initials: B
authors.lastname: Kutzner
authors.forename: James P
authors.initials: JP
authors.lastname: McNamee
authors.forename: Pascale V
authors.initials: PV
authors.lastname: Bellier
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Wilkins
mesh_terms: D000512:Alpha Particles; D000576:Americium / Q000633:toxicity; D002478:Cells, Cultured; D004249:DNA Damage; D004781:Environmental Exposure; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation / Q000528:radiation effects
chemical_list: D006657:Histones; D000576:Americium