Characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure.
Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0091828&type=printable |
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| _version_ | 1850026566349750272 |
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| author | Reuben Thomas Alan E Hubbard Cliona M McHale Luoping Zhang Stephen M Rappaport Qing Lan Nathaniel Rothman Roel Vermeulen Kathryn Z Guyton Jennifer Jinot Babasaheb R Sonawane Martyn T Smith |
| author_facet | Reuben Thomas Alan E Hubbard Cliona M McHale Luoping Zhang Stephen M Rappaport Qing Lan Nathaniel Rothman Roel Vermeulen Kathryn Z Guyton Jennifer Jinot Babasaheb R Sonawane Martyn T Smith |
| author_sort | Reuben Thomas |
| collection | DOAJ |
| description | Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from <1 ppm to >10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings. |
| format | Article |
| id | doaj-art-8a26ea5b2a6c482c949a17c23b93901b |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-8a26ea5b2a6c482c949a17c23b93901b2025-08-20T03:00:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9182810.1371/journal.pone.0091828Characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure.Reuben ThomasAlan E HubbardCliona M McHaleLuoping ZhangStephen M RappaportQing LanNathaniel RothmanRoel VermeulenKathryn Z GuytonJennifer JinotBabasaheb R SonawaneMartyn T SmithBenzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML). Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC), we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from <1 ppm to >10 ppm) compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering) exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0091828&type=printable |
| spellingShingle | Reuben Thomas Alan E Hubbard Cliona M McHale Luoping Zhang Stephen M Rappaport Qing Lan Nathaniel Rothman Roel Vermeulen Kathryn Z Guyton Jennifer Jinot Babasaheb R Sonawane Martyn T Smith Characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure. PLoS ONE |
| title | Characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure. |
| title_full | Characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure. |
| title_fullStr | Characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure. |
| title_full_unstemmed | Characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure. |
| title_short | Characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure. |
| title_sort | characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0091828&type=printable |
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