Response of human lymphoblastoid cells to HZE (iron ions) or gamma-rays
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Sally Amundson
PROVIDER: E-GEOD-16518 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
p53-independent downregulation of histone gene expression in human cell lines by high- and low-let radiation.
Meador Jarah A JA Ghandhi Shanaz A SA Amundson Sally A SA
Radiation research 20110426 6
Using microarrays to analyze differential gene expression as a function of p53 status and radiation quality, we observed downregulation of a large set of histone genes in p53 wild-type TK6 cells 24 h after exposure to equitoxic doses of high-LET (1.67 Gy 1 GeV/amu (56)Fe ions) or low-LET (2.5 Gy γ rays) radiation. Quantitative real-time PCR of specific subtypes of core (H2A, H2B, H3 and H4) and linker (H1) histones confirmed this result. DNA synthesis and histone gene expression are tightly coor ...[more]
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE16518: Response of human lymphoblastoid cells to HZE (iron ions) or gamma-rays GSE16519: Response of human lymphoblastoid cells to activated medium Refer to individual Series
2011-04-01 | E-GEOD-16525 | biostudies-arrayexpress
Project description:Transcriptional profiling of human lymphoblastoid TK6 cells comparing mock irradiaed cells resuspended in fresh untreated RPMI 1640 medium with cells resuspended in medium activated by exposure to 2.5 Gy HZE (1 GeV/amu iron ions accelerated at the NASA Space Research Laboratory (NSRL) of Brookhaven National Laboratory). Two-condition experiment, mock irradiated vs. cells exposed to activated medium. 3 biological replicates were independently grown and harvested during three different runs at the NSRL. One replicate per array.
2011-04-01 | E-GEOD-16519 | biostudies-arrayexpress
Project description:The 60 cell lines of the NCI Anti-Cancer Drug Screen (NCI60) constitute the most extensively characterized in vitro cancer cell model, and have been tested for sensitivity to over 100,000 potential chemotherapy agents. We have used the NCI60 cell lines and three additional lymphoblast lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonogenic survival, apoptosis induction, and gene expression response by microarray analysis. While several studies have measured relative basal gene expression in the NCI60, this is the first comparison of large-scale gene expression changes in response to genotoxic stress. We found genes differentially regulated in cells with low survival after 2 or 8 Gy γ-rays. In contrast to reported basal gene expression patterns, little tissue-of-origin effect was detected in the radiation response pattern of gene expression, with the exception of lymphoblastoid cell lines. The most striking patterns in the radiation data were a set of genes upregulated preferentially in the p53 wild-type lines, and a set of cell-cycle regulatory genes strongly down-regulated across the entire NCI60 panel. The response of these genes to γ-rays appears to be unaffected by the myriad of genetic differences across this very diverse cell set, and represents the most universal gene expression response to ionizing radiation yet observed. Cells were exposed to 8Gy and gene expression ratios between untreated (Cy5) cells and exposed cells (Cy3) were measured four hours later
2010-05-27 | E-GEOD-7505 | biostudies-arrayexpress
Project description:Plants exhibit a robust transcriptional response to gamma radiation which includes the induction of transcripts required for homologous recombination and the suppression of transcripts that promote cell cycle progression. Various DNA damaging agents induce different spectra of DNA damage as well as M-bM-^@M-^\collateralM-bM-^@M-^] damage to other cellular components and therefore are not expected to provoke identical responses by the cell. Here we study the effects of two different types of ionizing radiation (IR) treatment, HZE (1 GeV Fe26+ high mass, high charge, and high energy relativistic particles) and gamma photons, on the transcriptome of Arabidopsis thaliana seedlings. Both types of IR induce small clusters of radicals that can result in the formation of double strand breaks (DSBs), but HZE also produces linear arrays of extremely clustered damage. We performed these experiments across a range of time points (1.5-24 h after irradiation) in both wild-type plants and in mutants defective in the DSB-sensing protein kinase ATM. The two types of IR exhibit a shared double strand break-repair-related damage response, although they differ slightly in the timing, degree, and ATM-dependence of the response. The ATM-dependent, DNA metabolism-related transcripts of the M-bM-^@M-^\DSB responseM-bM-^@M-^] were also induced by other DNA damaging agents, but were not induced by conventional stresses. Both Gamma and HZE irradiation induced, at 24 h post-irradiation, ATM-dependent transcripts associated with a variety of conventional stresses; these were overrepresented for pathogen response, rather than DNA metabolism. In contrast, only HZE-irradiated plants, at 1.5 h after irradiation, exhibited an additional and very extensive transcriptional response, shared with plants experiencing M-bM-^@M-^\extended night.M-bM-^@M-^] This response was not apparent in gamma-irradiated plants. We treated 5-day-old WT and atm-1 seedlings of Arabidopsis thaliana with 100 Gy of Gamma radiation (over a span of 15 minutes) or 30 Gy of HZE (over a span of approximately 12 minutes). Gamma irradiations were completed at 8:40 am, while HZE irradiations were conducted in two runs (due to space limitations) which were completed at 1:09 and 1:28pm respectively. Gamma treated seedlings were sampled at 10:10 am, 11:40 am, 2:55 pm, 8:40 pm, and 8:40 am. HZE treated seedlings were sampled at 2:39 pm, 4:09 pm, 7:24 pm, 1:09 am, and 1:09 pm. Un-irradiated WT and atm-1 control seedlings were sampled at 10:45 am on Day #1 and 9:15 am on Day #2. There are a total of 22 experimental or control conditions, with two replicates per condition, yielding 44 samples overall.
2014-09-18 | E-GEOD-61484 | biostudies-arrayexpress
Project description:Transcriptional profiling of human lymphoblastoid TK6 cells comparing mock irradiated cells with cells exposed 24 hours previously to 1.67 Gy HZE (1 GeV/amu iron ions accelerated at the NASA Space Research Laboratory (NSRL) of Brookhaven National Laboratory) or 2.5 Gy 137Cs gamma rays.
2011-04-01 | GSE16518 | GEO
Project description:In this study, to delineate the radiation-induced changes in miRNAs and protein cargo, we established the microRNA and proteome profiles of plasma EVs collected from mice that had been sham- (SI), whole body (WBI), or partial body irradiated (PBI) with 2 Gy X-rays 24 hours before. The radiation-induced changes in the miRNA and protein composition of EVs can influence the stress response of distant cells by propagating damaging or protective signals. Testing EVs in functional assays may be a read out of the multiple radiation-induced signaling networks, crucial for gaining an understanding of the EVs properties. Therefore, to functionally elucidate the pathophysiological changes in the contents of EVs induced by irradiation, we here investigated the EV-induced cellular responses in vivo, by injecting WBI, PBI and SI plasma-derived EVs in the cerebellum of neonatal mice, highly susceptible to radiation injury, and evaluating the level of apoptosis.
2022-03-10 | PXD026408 | Pride
Project description:We examined molecular responses using transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) proton (56Fe) particles 1, 3, 7, 14 and 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the radiation (IR) response, and time after exposure with 56Fe-IR showing the greatest level of gene modulation. 1H-IR exposures showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Individual transcription factors were inferred to be active at 1, 3, 7, 14 and 28 days after exposure. Validation of the signal transduction network by protein analysis showed that particle IR clearly regulates a long lived signaling mechanism for p38 MAPK signaling and NFATc4 activation. Electrophoresis mobility shift assays supported the role of additional key transcription factors GATA-4, STAT-3 and NF-κB as regulators of the response at specific time points. These data suggest that the molecular response to 56Fe-IR is unique and shows long-lasting gene expression in cardiomyocytes, up to 28 days after exposure. Additionally, proteins involved in signal transduction and transcriptional activation via DNA binding play a role in the response to high charge (Z) and energy (E) particles (HZE). Our study may have implications for NASAâs efforts to develop heart disease risk estimates for astronauts safety via identification of specific HZE-IR molecular markers and for patients receiving conventional and particle radiotherapy. Transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) proton (56Fe) particles 1, 3, 7, 14 and 28 days after exposure.
2016-07-03 | E-GEOD-68875 | biostudies-arrayexpress
Project description:We examined molecular responses using transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) iron (56Fe) particles 1, 3, 7, 14 and 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the radiation (IR) response, and time after exposure with 56Fe-IR showing the greatest level of gene modulation. 1H-IR exposures showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Individual transcription factors were inferred to be active at 1, 3, 7, 14 and 28 days after exposure. Validation of the signal transduction network by protein analysis showed that particle IR clearly regulates a long lived signaling mechanism for p38 MAPK signaling and NFATc4 activation. Electrophoresis mobility shift assays supported the role of additional key transcription factors GATA-4, STAT-3 and NF-κB as regulators of the response at specific time points. These data suggest that the molecular response to 56Fe-IR is unique and shows long-lasting gene expression in cardiomyocytes, up to 28 days after exposure. Additionally, proteins involved in signal transduction and transcriptional activation via DNA binding play a role in the response to high charge (Z) and energy (E) particles (HZE). Our study may have implications for NASAâ??s efforts to develop heart disease risk estimates for astronauts safety via identification of specific HZE-IR molecular markers and for patients receiving conventional and particle radiotherapy. Transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) iron (56Fe) particles 1, 3, 7, 14 and 28 days after exposure.
2016-07-03 | E-GEOD-68874 | biostudies-arrayexpress
Project description:The bystander effect from ionizing radiation consists of cellular responses generated from unirradiated cells to the irradiation of their neighbors. The bystander effect can lead to DNA damage and genomic instability in the affected cells. This non-targeted effect of radiation has received attention due to its potential implications for cancer therapy and radiation protection. Although studied extensively, a complete understanding of its molecular mechanism is the subject of ongoing research. While many studies have targeted specific factors which are suggested to be involved in the bystander effect, few have looked at whole genome gene expression in bystander cells. Furthermore, even fewer studies have looked at the expression in noncancerous human cell lines. In this study we have used a genome-wide microarray approach to investigate transcriptional responses in irradiated and bystander immortalized human fibroblasts following 0.1 Gy ?-particle irradiation. Total RNA was isolated from F11hTERT fibroblasts irradiated with 0.1 Gy ?-particles and bystander fibroblasts receiving medium from control (sham irradiated) and irradiated cells (0.1 Gy). RNA was isolated 4, 8 and 26 h after irradiation.
2011-09-13 | E-GEOD-32091 | biostudies-arrayexpress
Project description:Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age at exposure and their underlying mechanisms remain unclear. We analyzed the mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). T-cell lymphoma incidence did not show any statistical differences among three irradiated groups; however, the frequency of loss of heterozygosity on chromosomes 11 and 19 showed opposing correlations with age at exposure. Ikaros on chromosome 11 was mutated frequently in the young adultâ??irradiation group (63%; 5/8), frequently incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik11, which lacks two of the four zincâ??finger domains important for DNA binding). Pten on chromosome 19 was mutated more frequently in tumors from infant- (67%; 10/15) compared with young adult-irradiated mice (13%; 1/8, P = 0.041). Despite the presence of homozygous Pten mutations, DNA copy number was unchanged in the infant-irradiation group, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Taken together, our findings demonstrate that while deletions on chromosome 11 affecting the Ikaros locus are a prominent feature of young adult irradiation-induced T-cell lymphoma, tumors arising after infant irradiation suffer a second hit in the Pten gene by chromosome mis-segregation or recombination. This is the first report showing age-at-exposure associated radiation-induced genomic alterations in two key tumor suppressor genes linked to T-cell lymphomagenesis. These data are important for considering the risks associated with childhood exposure to radiation. 38 T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting at different ages (Infant: 1 week old (15 tumors), Adolescent: 4 weeks old (13 tumors), Young adult: 8 weeks old (10 tumors)) were analyzed.
2015-11-12 | E-GEOD-63349 | biostudies-arrayexpress