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Whole blood gene expression in female Balb/c mice following 2-week Pb exposure and subsequent 2-week recovery period

ABSTRACT: Background: Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. Methodology/Principal Finding: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. Conclusions/Significance: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway.

ORGANISM(S): Mus musculus

PROVIDER: GSE28261 | GEO | 2011/03/30

SECONDARY ACCESSION(S): PRJNA139789

REPOSITORIES: GEO

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Whole blood gene expression in female Balb/c mice following 2-week Pb exposure and subsequent 2-week recovery period

Project description:Background: Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. Methodology/Principal Finding: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. Conclusions/Significance: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway. We isolate total RNA from 72 mouse whole blood samples. These included samples following a 2-week exposure to lead acetate trihydrate (untreated controls = 7; Low Pb 5ug/mL drinking water = 15; High Pb 50ug/mL drinking water = 15) and additional samples following a 2-week recovery period with plain drinking water (untreated controls = 7; Low Pb group = 15; High Pb group = 13).

2011-03-30 | E-GEOD-28261 | biostudies-arrayexpress

Gene expression signatures that predict radiation exposure (mouse)

Project description:Gene expression analysis of peripheral blood leukocytes (PB MNCs) to develop expression profiles that accurately reflect prior radiation exposure. Keywords: Comparative, exposure dosage, C57BI6 Murine Irradiation Studies We have made use of gene expression analysis of peripheral blood mononuclear cells (PB MNCs) to develop expression profiles that accurately reflect prior radiation exposure. Importantly, we demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, ranging from 50 cGy to 1000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from non-irradiated samples with an accuracy of 90%, sensitivity of 85% and specificity of 94%. We further demonstrate that a radiation profile developed in the mouse can correctly distinguish PB samples from irradiated and non-irradiated human patients with an accuracy of 77%, sensitivity of 82% and specificity of 75%. Taken together, these data demonstrate that molecular profiles can be generated which are highly predictive of different levels of radiation exposure in mice and humans. Mouse Dataset only

2010-06-11 | E-GEOD-6873 | biostudies-arrayexpress

Hippocampal methylome of rats exposed to lead at different developmental stages

Project description:Developmental lead (Pb) exposure results in persistent cognitive/behavioral impairments as well as an elevated risk for developing a variety of diseases in later life. Environmental exposures during development can result in a variety of epigenetic changes, including alterations in DNA methylation, that can influence gene expression patterns and affect the function and development of the nervous system. The present promoter-based methylation microarray profiling study explored the extent to which developmental Pb exposure may modify the methylome of a brain region, hippocampus, known to be sensitive to the effects of Pb exposure. Male and female Long Evans rats were exposed to 0 ppm, 150 ppm, 375 ppm, or 750 ppm Pb through perinatal exposures (gestation through lactation), early postnatal exposures (birth through weaning), or long-term postnatal exposures (birth through postnatal day 55). Results showed a significant contribution of sex to the hippocampal methylome and effects of Pb exposure level, with non-linear dose response effects on methylation. Surprisingly, the developmental period of exposure contributed only a small amount of variance to the overall data and gene ontology (GO) analysis revealed the largest number of overrepresented GO terms in the groups with the lowest level of exposure. The highest number of significant differentially methylated regions was found in females exposed to Pb at the lowest exposure level. Our data reinforce the significant effect that low level Pb exposure may have on gene-specific DNA methylation patterns in brain and that this occurs in a sex-dependent manner. NimbleGen Rat CpG Island plus RefSeq Promoter 720k array

2018-10-30 | GSE106323 | GEO

Gene expression signatures that predict radiation exposure (mouse)

2007-03-01 | GSE6873 | GEO

Specific, Durable and Accurate Gene Expression Signatures of Radiation Response in Mice and Humans

Project description:Previous work has demonstrated the potential for peripheral blood (PB) gene expression profiling for the detection of disease or environmental exposures. We have sought to determine the impact of several variables on the PB gene expression profile of an environmental exposure, ionizing radiation, and to determine the specificity of the PB signature of radiation versus other genotoxic stresses. Keywords: peripheral blood, gene expression study, radiation reponse We have sought to determine the impact of several variables on the PB gene expression profile of an environmental exposure, ionizing radiation, and to determine the specificity of the PB signature of radiation versus other genotoxic stresses. Neither genotype differences nor the time of PB sampling caused any lessening of the accuracy of PB signatures to predict radiation exposure, but sex difference did influence the accuracy of the prediction of radiation exposure at the lowest level (50 cGy). A PB signature of sepsis was also generated and both the PB signature of radiation and the PB signature of sepsis were found to be 100% specific at distinguishing irradiated from septic animals. We also identified human PB signatures of radiation exposure and chemotherapy treatment which distinguished irradiated patients and chemotherapy-treated individuals within a heterogeneous population with accuracies of 90% and 81%, respectively. Human and Murine samples used in models Peripheral blood was collected from patients prior to and 6 hrs following total body irradiation with 150 to 200 cGy as part of their pre-transplantation conditioning. For additional comparison, peripheral blood was obtained from healthy volunteers and an additional cohort of patients prior to and 6 hrs following the initiation of alkylator-based chemotherapy alone (without radiotherapy).

2010-05-17 | E-GEOD-10640 | biostudies-arrayexpress

Gene expression signatures that predict radiation exposure (human)

2007-03-01 | GSE6871 | GEO

Mapping the effects of developmental lead (Pb) exposure on the hippocampus with single cell analysis

Project description:Lead (Pb) exposure is ubiquitous with permanent neurodevelopmental effects. The hippocampus brain region is involved in learning and memory with heterogeneous cellular composition. The hippocampus cell type-specific responses to Pb are unknown. This experiement sought to examine perinatal Pb treatment effects on adult hippocampus gene expression, at the level of individual cells. In mice perinatally exposed to control water or a human physiologically-relevant level (32 ppm in maternal drinking water) of Pb, two weeks prior to mating through weaning, we tested for hippocampus gene expression and cellular differences at 5-months of age.

2020-06-04 | GSE151723 | GEO

Dose-response modeling of early molecular and cellular key events in CAR-mediated hepatocarcinogenesis pathway

Project description:Male and female CD-1 mice were administered dietary Phenobarbital for 2 or 7 days. In-life, enzyme activity, cell proliferation, genomic analysis, and Bench-mark dose modeling was carried out. The goal was to exmaine low-dose PB effects on early key events in CAR-mediated hepatocarcinogenesis. PB at 0, 0.15, 1.5, 15, 75, or 150 mg/kg-day for 2 or 7 days to characterize multiple apical and molecular endpoints.

2014-02-01 | E-GEOD-54597 | biostudies-arrayexpress

Influence of Water Chemistry on Toxicogenomics of Chronic Lead Toxicity to the Fathead Minnow (Pimephales promelas)

Project description:Despite major successes in reducing the risks of lead (Pb) exposure over the past few decades, two issues of considerable importance remain unresolved: (1) how differences in water chemistry influence acute and chronic Pb toxicity, and (2) the elucidation of specific toxic mechanisms and modes of action (MOA). To more clearly define the water chemistry parameters mediating Pb toxicity we evaluated the effects of hardness (as CaSO4) and DOC (as humic acid (HA)) during chronic (150d) exposures to the fathead minnow (Pimephales promelas). Traditional toxicological endpoints were examined alongside gene expression analyses to help clarify the underlying mechanisms and MOA of Pb toxicity and to identify robust molecular markers of exposure and effect. Keywords: time course, chronic lead (Pb) exposure

2008-04-07 | GSE8404 | GEO

Dose-response modeling of early molecular and cellular key events in CAR-mediated hepatocarcinogenesis pathway

2014-02-01 | GSE54597 | GEO

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