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.

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Study IDST001918
Study TitleMetabolome-wide association study of occupational exposure to benzene
Study SummaryBenzene 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
DepartmentEnvironmental Medicine and Public Health
LaboratoryHigh Resolution Exposomics
Last NameWalker
First NameDouglas
AddressAtran Building RM AB3-39, 1428 Madison Ave, New York, NY, 10029, USA
Emaildouglas.walker@mssm.edu
Phone1-212-241-4392
Submit Date2021-08-26
Num Groups3
Total Subjects58
Num Males28
Num Females30
PublicationsN 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 AvailableYes
Raw Data File Type(s)mzXML, raw(Thermo)
Analysis Type DetailLC-MS
Release Date2021-10-02
Release Version1
Douglas Walker Douglas Walker
https://dx.doi.org/10.21228/M8F70B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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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
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