Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA127045 | ENA |
REPOSITORIES: ENA
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Project description:Human toxicogenomic studies to date have been of limited size, have mainly addressed exposures at the upper end of typical ranges of human exposure, and have often lacked precise, individual estimates of exposure. Previously, we identified genes associated with exposure to high (>10 ppm) levels of the leukemogen, benzene, through transcriptomic analyses of blood cells from small numbers of occupationally exposed workers. Here, we have expanded the study to 125 workers exposed to a wide range of benzene levels, including <1 ppm. Study design, and analysis with a mixed effects model, removed sources of biological and experimental variability and revealed highly significant widespread perturbation of gene expression at all exposure levels. Benzene is an established cause of acute myeloid leukemia (AML), and may cause one or more lymphoid malignancies in humans. Interestingly, acute myeloid leukemia was among the most significant pathways impacted by benzene exposure in the present study. Further, at most exposure levels, immune response pathways including T cell receptor signaling, B cell receptor signaling, and Toll like receptor signaling were impacted, providing support for the biological plausibility of an association between lymphoma and benzene exposure. We also identified a 16-gene expression signature modified by all levels of benzene exposure, comprising genes with roles in immune response, inflammatory response, cell adhesion, cell-matrix adhesion, and blood coagulation. Overall, these findings support, and expand upon, our current understanding of the mechanisms by which benzene may induce hematotoxicity, leukemia and lymphoma. Furthermore, this study shows that with good study design and analysis, transcriptome profiling of the blood of chemically-exposed humans can identify relevant biomarkers across a range of exposures and inform about potential associations with disease risks. Key words: occupational exposure 29 workers exposed to <<1ppm benzene at most dosimetry reading over a 14-month period (Very Low), 30 exposed to average <1ppm (Low), 11 exposed to 5-10 ppm (High), 13 exposed to >10 ppm (Very High), and 42 unexposed controls (Control) who were frequency-matched to these subjects on the basis of age and gender were analyzed (technical replicates on some subjects, see SubjectID/description).
2011-05-14 | E-GEOD-21862 | biostudies-arrayexpress
Project description:Human toxicogenomic studies to date have been of limited size, have mainly addressed exposures at the upper end of typical ranges of human exposure, and have often lacked precise, individual estimates of exposure. Previously, we identified genes associated with exposure to high (>10 ppm) levels of the leukemogen, benzene, through transcriptomic analyses of blood cells from small numbers of occupationally exposed workers. Here, we have expanded the study to 125 workers exposed to a wide range of benzene levels, including <1 ppm. Study design, and analysis with a mixed effects model, removed sources of biological and experimental variability and revealed highly significant widespread perturbation of gene expression at all exposure levels. Benzene is an established cause of acute myeloid leukemia (AML), and may cause one or more lymphoid malignancies in humans. Interestingly, acute myeloid leukemia was among the most significant pathways impacted by benzene exposure in the present study. Further, at most exposure levels, immune response pathways including T cell receptor signaling, B cell receptor signaling, and Toll like receptor signaling were impacted, providing support for the biological plausibility of an association between lymphoma and benzene exposure. We also identified a 16-gene expression signature modified by all levels of benzene exposure, comprising genes with roles in immune response, inflammatory response, cell adhesion, cell-matrix adhesion, and blood coagulation. Overall, these findings support, and expand upon, our current understanding of the mechanisms by which benzene may induce hematotoxicity, leukemia and lymphoma. Furthermore, this study shows that with good study design and analysis, transcriptome profiling of the blood of chemically-exposed humans can identify relevant biomarkers across a range of exposures and inform about potential associations with disease risks. Key words: occupational exposure
2011-05-14 | GSE21862 | GEO
Project description:The effect of benzene exposure on peripheral blood mononuclear cell (PBMC) gene expression was examined in a population of shoe-factory workers with well-characterized occupational exposures to benzene. We compared data from two microarray platforms (Illumina and Affymetrix). Keywords: occupational exposure
2009-05-11 | GSE9569 | GEO
Project description:Benzene, a natural component of petroleum products, is a known hematotoxic and leukemogenic agent. The haematotoxic effect and excess leukemia has been reported below 1 ppm, an exposure level previously considered not to cause any health effects. Gene expression studies suggest that benzene affects genes involved in AML and immune response pathways in a supra-linear manner, and at exposure levels as low as 0.1 ppm benzene. An increased risk of haematopoietic malignancies and altered gene expression also at exposure below 1 ppm is compatible with the emerging knowledge of a non-linear metabolism of benzene, favouring production of a greater proportion of toxic metabolites in subjects exposed to benzene concentrations below 1 ppm than in heavily exposed workers. In the present study, we investigated whether workers found to have a dose-dependent decline in relevant immune cells after benzene-exposure deviated from the unexposed referents in global gene expression changes in whole blood samples, and whether any pathways or genes previously reported in similar low-dose gene expression studies were differentially affected. The study population comprised eight benzene-exposed petroleum workers and five referents deemed unexposed to benzene recruited from the catering section on the same offshore installation (for sampling strategy, see sampling protocol). The two groups significantly differed in age. The dataset was therefore balanced for age by excluding workers at age <35 and >55 in the data modelling to identify significant genes.
2017-10-19 | E-MTAB-5331 | biostudies-arrayexpress
Project description:Previously, using microarrays and mRNA-Sequencing (mRNA-Seq) we found that occupational exposure to a range of benzene levels perturbed gene expression in peripheral blood mononuclear cells. In the current study, we sought to identify gene expression biomarkers predictive of benzene exposure below 1 part per million (ppm), the occupational standard in the U.S. First, we used the nCounter platform to validate altered expression of 30 genes in 33 unexposed controls and 57 subjects exposed to benzene (<1 to ≥5 ppm). Second, we used SuperLearner (SL) to identify a minimal number of genes for which altered expression could predict <1 ppm benzene exposure, in 44 subjects with a mean air benzene level of 0.55±0.248 ppm (minimum 0.203ppm). nCounter and microarray expression levels were highly correlated (coefficients >0.7, p<0.05) for 26 microarray-selected genes. nCounter and mRNA-Seq levels were poorly correlated for 4 mRNA-Seq-selected genes. Using negative binomial regression with adjustment for covariates and multiple testing, we confirmed differential expression of 23 microarray-selected genes in the entire benzene-exposed group, and 27 genes in the <1 ppm-exposed subgroup, compared with the control group. Using SL, we identified 3 pairs of genes that could predict <1 ppm benzene exposure with cross-validated AUC estimates >0.9 (p<0.0001) and were not predictive of other exposures (nickel, arsenic, smoking, stress). The predictive gene pairs are PRG2/CLEC5A, NFKBI/CLEC5A, and ACSL1/CLEC5A. They play roles in innate immunity and inflammatory responses. Using nCounter and SL, we validated the altered expression of multiple mRNAs by benzene and identified gene pairs predictive of exposure to benzene at levels below the US occupational standard of 1ppm.
2018-09-06 | GSE119533 | GEO
Project description:Benzene is a ubiquitous environmental pollutant and an established human hematotoxicant and leukemogen. New insights into the pathogenesis of benzene hematotoxicity are urgently needed. Long non-coding RNA（lncRNA）can regulate gene expression and widely participate in the various physiological and pathological processes. Microarray analysis was used to identify the differentially expressed lncRNA and mRNA that were likely to be critical for benzene hematotoxicity. An integrated analysis of lncRNA and mRNA expression profiles was performed to identify key hub genes, pathways and biological processes. Peripheral blood samples were randomly obtained from four patients of chronic benzene poisoning, three benzene-exposed workers and three health controls without benzene exposure. The occupational history, age, gender, lifestyle such as smoking, drinking, recent drug use situation and medical history in each group were matched. Total RNA was extracted and an integrated analysis of lncRNA and mRNA expression profiles was performed by GeneChip Human Gene 2.0 ST Array (Affymetrix).
2015-07-27 | E-GEOD-50737 | biostudies-arrayexpress
Project description:To identify potential methylation biomarkers in occupationally benzene-exposed individuals and to elucidate mechanisms of benzene hematotoxicity.
2016-09-12 | GSE50967 | GEO
Project description:The effects of the aromatic hydrocarbons benzene and toluene on Nitrosomonas europaea, a nitrifying bacterium that plays an important role in the removal of nitrogen from wastewater treatment plants, were studied in batch reactors. Exposure to 20 M toluene and 40 M benzene resulted in a 50% reduction in nitrifying activity after 1 h. However, Affymetrix microarray experiments detected no significant changes in gene expression in toluene exposed cells. Cells exposed to benzene were found to up-regulate a gene cluster (NE 1545 - NE 1551). This gene cluster appears to be involved with fatty-acid metabolism, lipid and membrane protein biosynthesis. TEM experiments reveal that cells exposed to benzene decrease the thickness of their membrane and the membrane becomes more structured. Keywords: stress response, benzene, toluene
2008-02-13 | GSE10507 | GEO