Summary of Study ST001918
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001209. The data can be accessed directly via it's Project DOI: 10.21228/M8F70B This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST001918 |
| Study Title | Metabolome-wide association study of occupational exposure to benzene |
| Study Summary | Benzene is a recognized hematotoxin and leukemogen; however, its mechanism of action in humans remain unclear. To provide insight into the processes underlying benzene hematotoxicity, we performed high-resolution metabolomic (HRM) profiling of plasma collected from a cross-sectional study of 33 healthy workers exposed to benzene (median 8-hr time-weighted average exposure; 20 ppma), and 25 unexposed controls in Shanghai, China. Metabolic features associated with benzene were identified using a metabolome-wide association study (MWAS) that tested for the relationship between feature intensity and benzene exposure. MWAS identified 478 mass spectral features associated with benzene exposure at FDR<20%. Comparison to a list of 13 known benzene metabolites and metabolites predicted using a multi-component biotransformation algorithm showed five metabolites were detected, which included the known metabolites phenol and benzene diolepoxide. Metabolic pathway enrichment identified 41 pathways associated with benzene exposure, with altered pathways including carnitine shuttle, fatty acid metabolism, sulfur amino acid metabolism, glycolysis, gluconeogenesis, and branched chain amino acid metabolism. These results suggest disruption to fatty acid uptake, energy metabolism and increased oxidative stress, and point towards pathways related to mitochondrial dysfunction, which has previously been linked to benzene exposure in animal models and human studies. Taken together, these results suggest benzene exposure is associated with disruption of mitochondrial pathways, and provide promising, systems biology biomarkers for risk assessment of benzene-induced hematotoxicity in humans. |
| Institute | Icahn School of Medicine at Mount Sinai |
| Department | Environmental Medicine and Public Health |
| Laboratory | High Resolution Exposomics |
| Last Name | Walker |
| First Name | Douglas |
| Address | Atran Building RM AB3-39, 1428 Madison Ave, New York, NY, 10029, USA |
| douglas.walker@mssm.edu | |
| Phone | 1-212-241-4392 |
| Submit Date | 2021-08-26 |
| Num Groups | 3 |
| Total Subjects | 58 |
| Num Males | 28 |
| Num Females | 30 |
| Publications | N Rothman, R Vermeulen, L Zhang, W Hu, S Yin, SM Rappaport, MT Smith, DP Jones, M Rahman, Qing Lan, DI Walker. (2021). Metabolome-wide association study of occupational exposure to benzene. Carcinogenesis. In Review |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML, raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2021-10-02 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001209 |
| Project DOI: | doi: 10.21228/M8F70B |
| Project Title: | Metabolome-wide association study of occupational exposure to benzene |
| Project Summary: | Benzene is a recognized hematotoxin and leukemogen; however, its mechanism of action in humans remain unclear. To provide insight into the processes underlying benzene hematotoxicity, we performed high-resolution metabolomic (HRM) profiling of plasma collected from a cross-sectional study of 33 healthy workers exposed to benzene (median 8-hr time-weighted average exposure; 20 ppma), and 25 unexposed controls in Shanghai, China. Metabolic features associated with benzene were identified using a metabolome-wide association study (MWAS) that tested for the relationship between feature intensity and benzene exposure. MWAS identified 478 mass spectral features associated with benzene exposure at FDR<20%. Comparison to a list of 13 known benzene metabolites and metabolites predicted using a multi-component biotransformation algorithm showed five metabolites were detected, which included the known metabolites phenol and benzene diolepoxide. Metabolic pathway enrichment identified 41 pathways associated with benzene exposure, with altered pathways including carnitine shuttle, fatty acid metabolism, sulfur amino acid metabolism, glycolysis, gluconeogenesis, and branched chain amino acid metabolism. These results suggest disruption to fatty acid uptake, energy metabolism and increased oxidative stress, and point towards pathways related to mitochondrial dysfunction, which has previously been linked to benzene exposure in animal models and human studies. Taken together, these results suggest benzene exposure is associated with disruption of mitochondrial pathways, and provide promising, systems biology biomarkers for risk assessment of benzene-induced hematotoxicity in humans. |
| Institute: | Icahn School of Medicine at Mount Sinai |
| Department: | Environmental Medicine and Public Health |
| Laboratory: | High Resolution Exposomics |
| Last Name: | Walker |
| First Name: | Douglas |
| Address: | Atran Building RM AB3-39, 1428 Madison Ave, New York, NY, 10029, USA |
| Email: | douglas.walker@mssm.edu |
| Phone: | 1-212-241-4392 |
| Funding Source: | This work was supported by funds received from the National Institute of Environmental Health Sciences (ES026561, ES023515, ES019776, ES028903), the National Institutes of Health Office of the Director (OD018006), EU-H2020 (874627), EXPOSOME-NL (NWO grant number 024.004.017) and intramural funds received from the National Cancer Institute. |
| Project Comments: | This data was submitted in support of |
| Publications: | N Rothman, R Vermeulen, L Zhang, W Hu, S Yin, SM Rappaport, MT Smith, DP Jones, M Rahman, Qing Lan, DI Walker. (2021). Metabolome-wide association study of occupational exposure to benzene. Carcinogenesis. In Review |
