Gene Expression Profiles in Human Lymphocytes Irradiated In Vitro with Low Doses of Gamma Rays

Fachin, Ana Lúcia; Mello, Stephano S.; Sandrin-Garcia, Paula; Junta, Cristina M.; Donadi, Eduardo Antônio; Passos, Geraldo A. S.; Sakamoto-Hojo, Elza T.

doi:10.1667/rr0487.1

Cited by 61 publications

(45 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among the modulated genes, 16 genes had significant Y-intercepts in both independent cell lines based on linear regression analyses that excluded the sham group (as shown in Table 2); this finding provides strong suggestive evidence that transcription of these genes was induced at doses lower than 1 cGy. Our finding of significant transcript modulation changes induced by 10 cGy is consistent with prior findings [14,[33][34][35][36][37]53]. Also consistent with our findings, Jin and colleagues [38] reported non-linear transcription responses after low dose exposures.…”

Section: Shape Of the Transcript Dose Response Curvessupporting

confidence: 93%

“…We compared our radiation-responsive genes (Table1 and Table S1) with findings of other low-dose transcript studies [13,15,[33][34][35][36][37][38][39]41]. Using our 81-gene set, elevated GGH transcript was in common with the mouse brain findings [19], TNFRSF6 with ML-1 cells [13], SCAMP1 with keratinocytes [34] and RPL5 with HUVE cells [36].…”

Section: Comparison Of Results With Other Low-dose Transcript Data Setsmentioning

confidence: 99%

“…Also consistent with our findings, Jin and colleagues [38] reported non-linear transcription responses after low dose exposures. Non-linear dose-response relationships have previously been reported at higher doses for non-genomic endpoints, such as chromosome aberrations [57] and cell killing [58] after exposures to low-LET radiation, and more recently in a more limited study of low dose effects on transcript levels [35,37].…”

Section: Shape Of the Transcript Dose Response Curvesmentioning

confidence: 93%

“…Transcriptional profiling is a sensitive biomarker of radiation exposure and has been used to gain insight into the molecular mechanisms induced by low dose exposures in a variety of cell types: cell cultures of human myeloid cells [14,33], keratinocytes [34], lymphocytes [35], umbilical vein endothelial cells [36], lymphoblastoid cells [37], and mesenchymal stem cells [38]. Only a few studies investigated transcript profiles after in vivo low-dose exposures.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Wyrobek

Manohar

Krishnan

et al. 2011

Mutation Research/Genetic Toxicology and Environmental Mutagene

View full text Add to dashboard Cite

We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues.Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of ~80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.

show abstract

Section: Shape Of the Transcript Dose Response Curvessupporting

confidence: 93%

Section: Comparison Of Results With Other Low-dose Transcript Data Setsmentioning

confidence: 99%

Section: Shape Of the Transcript Dose Response Curvesmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Wyrobek

Manohar

Krishnan

et al. 2011

Mutation Research/Genetic Toxicology and Environmental Mutagene

View full text Add to dashboard Cite

show abstract

“…Recently, the role of Rad50 has been suggested in RIR using S. cerevisiae (Bala and Goel 2007). Elevated expression of Rad50 in low dose (0.50 Gy) irradiated human lymphocytes has also been reported (Fachin et al 2007). But no report demonstrated the expression of Mre11 and Rad50 in radio-adapted human lymphocytes.…”

Section: Thementioning

confidence: 99%

Modification in the Expression of MRE11/RAD50/NBS1 Complex in Low dose Irradiated Human Lymphocytes

Singh¹,

Bala

Kumar

et al. 2009

Dose-Response

View full text Add to dashboard Cite

Despite the fact that high doses of radiation are detrimental, low dose radiation (LDR) often protects the organism against a subsequent exposure of lethal doses of radiation. Present study was undertaken to understand the role of Mre11, Rad50 and Nbs1 genes in the low dose radio-adapted human peripheral blood mononuclear cells (PBMCs). Optimum time interval between low dose (0.07 Gy) and high dose (5.0 Gy) of 60Co-γ-radiation was observed to be 5.0 hours, at which PBMCs showed maximum LDR induced resistance (RIR). At cytogenetic level, micronuclei frequency was found to be reduced in LDR pre-irradiated PBMCs subsequently exposed to high dose radiation (HDR) as compared to controls. At transcriptional level, with reference to sham-irradiated cells significantly (p≤0.05) altered expression of Mre11, Rad50 and Nbs1 genes was observed in low dose irradiated cells. At protein level, Mre11, Rad50 and Nbs1 were enhanced significantly (p≤0.05) in low dose pre-irradiated cells subsequently exposed to high dose of radiation as compared to only high dose irradiated cells. Transcriptional as well as translational modulation in the expression of MRN complex components upon low dose irradiation may confer its participation in repair pathways, resulting in induced resistance.

show abstract

Metabolomic studies of radiation‐induced apoptosis of human leukocytes by capillary electrophoresis‐mass spectrometry and flow cytometry: Adaptive cellular responses to ionizing radiation

Lee

Britz‐McKibbin

2010

Electrophoresis

View full text Add to dashboard Cite

There is growing interest in the development of new methods for elucidating the biological effects of low-dose exposure to ionizing radiation (IR) on human health. Herein, we introduce a strategy for assessment of the impact of radiation-induced oxidative stress on the intra-cellular metabolism of human leukocytes. Untargeted metabolomic analyses were performed by CE-ESI-MS on irradiated leukocytes exposed to increasing doses of -radiation emitted from a Taylor source, which were subsequently incubated for 44 h to allow for cellular recovery. Flow cytometry with dual fluorescence staining revealed a major shift from early- to late-stage apoptosis associated with cell membrane permeability changes as radiation dosage was increased relative to the control, but with a significant attenuation measured at intermediate dose levels. CE-ESI-MS analysis of filtered white blood cell lysates was also performed to quantify changes associated with 22 intra-cellular metabolites, which were consistently measured in leukocytes across all radiation levels. Preliminary experiments demonstrated that there was an overall depletion in metabolites with extended exposure to IR; however, there was a non-linear upregulation of specific metabolites at the 4 Gy level relative to pre-irradiated levels, notably for arginine, glutamine, creatine, proline and reduced glutathione. Our studies demonstrate that leukocytes require a minimum threshold level of IR to induce a cytoprotective response in metabolism associated with antioxidant defense, energy homeostasis and cell signaling, which is relevant to improved understanding of the mechanisms of oxidative stress in radiobiology and cancer therapy.

show abstract

Gene Expression Profiles in Human Lymphocytes Irradiated In Vitro with Low Doses of Gamma Rays

Cited by 61 publications

References 65 publications

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Modification in the Expression of MRE11/RAD50/NBS1 Complex in Low dose Irradiated Human Lymphocytes

Metabolomic studies of radiation‐induced apoptosis of human leukocytes by capillary electrophoresis‐mass spectrometry and flow cytometry: Adaptive cellular responses to ionizing radiation

Contact Info

Product

Resources

About