title: Induction of cytokine gene expression in human thyroid epithelial cells irradiated with HZE particles (iron ions).
abstract: Gene expression profiles were examined using cDNA microarray technology in human thyroid epithelial (Htori-3) cells exposed to a low, non-toxic dose (10 cGy) of radiation from HZE particles in the form of iron ions in the absence or presence of selenomethionine (SeM). A total of 215 genes were differentially regulated 2 h after exposure to a 10-cGy dose of iron-ion radiation. In the microarray analysis, SeM had profound effects on the radiation-induced expression of several specific genes, which includes PLAU, IGFBP3, FOLR1, B4GALT1 and COL1A1. Of particular interest to us was a gene cluster, "secreted proteins", that was up-regulated after radiation exposure. Seven up-regulated genes of this gene cluster fall within the chemokine/cytokine gene cluster, namely, CXCL1, CXCL2, IL6, IL11, IL8, IL24 and TGFbeta2. In microarray studies, the radiation-induced up-regulated expression of some these genes encoding cytokine/chemokine proteins was significantly decreased by SeM treatment. For IL8, TGFbeta2, CXCL1 and CXCL2, these observations were validated by qPCR techniques. It is concluded that SeM can regulate ionizing radiation-induced gene expression and may serve as an effective countermeasure for some of the acute inflammatory/immune responses induced by low-dose HZE-particle radiation.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Jenine K
authors.initials: JK
authors.lastname: Sanzari
authors.forename: Manunya
authors.initials: M
authors.lastname: Nuth
authors.forename: Ann R
authors.initials: AR
authors.lastname: Kennedy
mesh_terms: D018480:Astronauts; D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D005118:Extraterrestrial Environment; D020869:Gene Expression Profiling; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D011829:Radiation Dosage; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012645:Selenomethionine / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology*; D015533:Transcriptional Activation / Q000187:drug effects / Q000528:radiation effects*
chemical_list: D016207:Cytokines; D012645:Selenomethionine; D007501:Iron