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:
Combined analysis:
| Analysis ID | AN003116 | AN003117 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | Reversed phase |
| Chromatography system | Thermo Dionex Ultimate 3000 | Thermo Dionex Ultimate 3000 |
| Column | Waters XBridge BEH Amide XP HILIC (50 x 2.1mm,2.5m) | Higgins endcapped C18 (50 x 2.1mm,3um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive HF hybrid Orbitrap | Thermo Q Exactive HF hybrid Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Peak area | Peak area |
Chromatography:
| Chromatography ID: | CH002301 |
| Chromatography Summary: | HILIC–positive chromatography method summary The HILIC column is operated parallel to reverse phase column for simultaneous analytical separation and column flushing through the use of a dual head HPLC pump equipped with 10-port and 6-port switching valves. During operation of HILIC separation method, the MS is operated in positive ion mode and 10 μL of sample is injected onto the HILIC column while the reverse phase column is flushing with wash solution. Flow rate is maintained at 0.35 mL/min until 1.5 min, increased to 0.4 mL/min at 4 min and held for 1 min. Solvent A is 100% LC-MS grade water, solvent B is 100% LC-MS grade acetonitrile and solvent C is 2% formic acid (v/v) in LC-MS grade water. Initial mobile phase conditions are 22.5% A, 75% B, 2.5% C hold for 1.5 min, with linear gradient to 77.5% A, 20% B, 2.5% C at 4 min, hold for 1 min, resulting in a total analytical run time of 5 min. During the flushing phase (reverse phase analytical separation), the HILIC column is equilibrated with a wash solution of 77.5% A, 20% B, 2.5% C |
| Methods Filename: | EmoryUniversity_HRM-QEHF_DC5min_092017_v1.pdf |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Waters XBridge BEH Amide XP HILIC (50 x 2.1mm,2.5m) |
| Flow Gradient: | Initial mobile phase conditions are 22.5% A, 75% B, 2.5% C hold for 1.5 min, with linear gradient to 77.5% A, 20% B, 2.5% C at 4 min, hold for 1 min, resulting in a total analytical run time of 5 min. |
| Solvent A: | 100% water(A), 100% acetonitrile(B), 100% water; 2% formic acid(C) |
| Solvent B: | 100% water(A), 100% acetonitrile(B), 100% water; 2% formic acid(C) |
| Chromatography Type: | HILIC |
| Chromatography ID: | CH002302 |
| Chromatography Summary: | C18–negative chromatography method summary The C18 column is operated parallel to the HILIC column for simultaneous analytical separation and column flushing through the use of a dual head HPLC pump equipped with 10-port and 6-port switching valves. During operation of the C18 method, the MS is operated in negative ion mode and 10 μL of sample is injected onto the C18 column while the HILIC column is flushing with wash solution. Flow rate is maintained at 0.4 mL/min until 1.5 min, increased to 0.5 mL/min at 2 min and held for 3 min. Solvent A is 100% LC-MS grade water, solvent B is 100% LC-MS grade acetonitrile and solvent C is 10mM ammonium acetate in LC-MS grade water. Initial mobile phase conditions are 60% A, 35% B, 5% C hold for 0.5 min, with linear gradient to 0% A, 95% B, 5% C at 1.5 min, hold for 3.5 min, resulting in a total analytical run time of 5 min. During the flushing phase (HILIC analytical separation), the C18 column is equilibrated with a wash solution of 0% A, 95% B, 5% C until 2.5 min, followed by an equilibration solution of 60% A, 35% B, 5% C for 2.5 min. |
| Methods Filename: | EmoryUniversity_HRM-QEHF_DC5min_092017_v1.pdf |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Higgins endcapped C18 (50 x 2.1mm,3um) |
| Flow Gradient: | Initial mobile phase conditions are 60% A, 35% B, 5% C hold for 0.5 min, with linear gradient to 0% A, 95% B, 5% C at 1.5 min, hold for 3.5 min, resulting in a total analytical run time of 5 min. |
| Flow Rate: | 0.4 mL/min-0.5 mL/min |
| Solvent A: | 100% water(A), 100% acetonitrile(B), 10 mM ammonium acetate(C) |
| Solvent B: | 100% water(A), 100% acetonitrile(B), 10 mM ammonium acetate(C) |
| Chromatography Type: | Reversed phase |
