L-selenomethionine modulates high LET radiation-induced alterations of gene expression in cultured human thyroid cells

Stewart, Jelena; Ware, Jeffrey H.; Fortina, Paolo; Breaux, Jim; Gulati, Sandeep; Kennedy, Ann R.

doi:10.3892/or.16.3.569

Cited by 9 publications

(8 citation statements)

References 9 publications

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“…The exposure to 0.1 and 0.2 Gy of 56 Fe ion radiation induced significant differential expression of 196 and 610 genes, respectively, and the differential expression of 39% to 55% of these genes was abolished by the SeM treatment (298). Genes and functional pathways that were significantly up- or down-regulated by the 56 Fe ion irradiation in the absence, but not in presence, of SeM treatment have been summarized previously (297, 298). Of particular interest was a cluster of chemokine and cytokine genes, e.g., CXCL1, CXCL2, IL6, IL11, IL8, IL24 and TGFβ2, which showed increased expression after irradiation with 0.1 Gy of 1-GeV/n 56 Fe ions in the absence, but not in the presence, of 5 µM SeM in the medium before and during the radiation exposure (299).…”

Section: Countermeasures and Mitigation Of Space Radiation Damagementioning

confidence: 94%

“…In a separate study performed with cultured HTori-3 cells exposed to low doses (0.1 and 0.2 Gy) of 1-GeV/n 56 Fe ion radiation, treatment with 5 µM SeM in the medium for 24 hours prior to irradiation profoundly affected the radiation induced alterations in gene expression (297). The exposure to 0.1 and 0.2 Gy of 56 Fe ion radiation induced significant differential expression of 196 and 610 genes, respectively, and the differential expression of 39% to 55% of these genes was abolished by the SeM treatment (298).…”

Section: Countermeasures and Mitigation Of Space Radiation Damagementioning

confidence: 99%

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Biological effects of space radiation and development of effective countermeasures

Kennedy

2014

Life Sciences in Space Research

150

117

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As part of a program to assess the adverse biological effects expected from astronaut exposure to space radiation, numerous different biological effects relating to astronaut health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronaut vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), and survival, as well as long-term effects such as cancer and cataract development. A number of different countermeasures have been identified that can potentially mitigate or prevent the adverse biological effects resulting from exposure to space radiation.

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Section: Countermeasures and Mitigation Of Space Radiation Damagementioning

confidence: 94%

Section: Countermeasures and Mitigation Of Space Radiation Damagementioning

confidence: 99%

Biological effects of space radiation and development of effective countermeasures

Kennedy

2014

Life Sciences in Space Research

150

117

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“…Gene chips and cDNA were prepared in-house by the Penn Microarray Facility at the University of Pennsylvania School of Medicine as described previously (12). Briefly, 1 µg of total RNA was converted to first-strand cDNA using Superscript II reverse transcriptase primed by a poly(T) oligomer that incorporated the T7 promoter.…”

Section: Methodsmentioning

confidence: 99%

Induction of Cytokine Gene Expression in Human Thyroid Epithelial Cells Irradiated with HZE Particles (Iron Ions)

Sanzari¹,

Nuth²,

Kennedy³

2009

Radiation Research

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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.

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“…For example, as a result of these features, many studies on chromosomal change, RET/PTC rearrangement, adverse biological effects, and selenomethionine-mediated protection against these adverse biological effects have been performed [ 14 , 26 – 31 ]. However, gene expression profiling has only documented the alterations in gene expression caused by space radiation [ 29 – 30 ]; so far only the generation of RET/PTC rearrangements has been studied following exposure to γ-radiation [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Gene expression profiling in undifferentiated thyroid carcinoma induced by high-dose radiation

Bang¹,

Choi²,

Kim³

et al. 2016

Journal of Radiation Research

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Published gene expression studies for radiation-induced thyroid carcinogenesis have used various methodologies. In this study, we identified differential gene expression in a human thyroid epithelial cell line after exposure to high-dose γ-radiation. HTori-3 cells were exposed to 5 or 10 Gy of ionizing radiation using two dose rates (high-dose rate: 4.68 Gy/min, and low-dose rate: 40 mGy/h) and then implanted into the backs of BALB/c nude mice after 4 (10 Gy) or 5 weeks (5 Gy). Decreases in cell viability, increases in giant cell frequency, anchorage-independent growth in vitro, and tumorigenicity in vivo were observed. Particularly, the cells irradiated with 5 Gy at the high-dose rate or 10 Gy at the low-dose rate demonstrated more prominent tumorigenicity. Gene expression profiling was analyzed via microarray. Numerous genes that were significantly altered by a fold-change of >50% following irradiation were identified in each group. Gene expression analysis identified six commonly misregulated genes, including CRYAB, IL-18, ZNF845, CYP24A1, OR4N4 and VN1R4, at all doses. These genes involve apoptosis, the immune response, regulation of transcription, and receptor signaling pathways. Overall, the altered genes in high-dose rate (HDR) 5 Gy and low-dose rate (LDR) 10 Gy were more than those of LDR 5 Gy and HDR 10 Gy. Thus, we investigated genes associated with aggressive tumor development using the two dosage treatments. In this study, the identified gene expression profiles reflect the molecular response following high doses of external radiation exposure and may provide helpful information about radiation-induced thyroid tumors in the high-dose range.

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L-selenomethionine modulates high LET radiation-induced alterations of gene expression in cultured human thyroid cells

Cited by 9 publications

References 9 publications

Biological effects of space radiation and development of effective countermeasures

Biological effects of space radiation and development of effective countermeasures

Induction of Cytokine Gene Expression in Human Thyroid Epithelial Cells Irradiated with HZE Particles (Iron Ions)

Gene expression profiling in undifferentiated thyroid carcinoma induced by high-dose radiation

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