Systems biology of human benzene exposure

Luoping Zhang, Cliona M. McHale, Nathaniel Rothman, Guilan Li, Zhiying Ji, Roel Vermeulen, Alan E. Hubbard, Xuefeng Ren, Min Shen, Stephen M. Rappaport, Matthew North, Christine F. Skibola, Songnian Yin, Christopher Vulpe, Stephen J. Chanock, Martyn T. Smith, Qing Lan

Research output: Contribution to journalArticle

Abstract

Toxicogenomic studies, including genome-wide analyses of susceptibility genes (genomics), gene expression (transcriptomics), protein expression (proteomics), and epigenetic modifications (epigenomics), of human populations exposed to benzene are crucial to understanding gene-environment interactions, providing the ability to develop biomarkers of exposure, early effect and susceptibility. Comprehensive analysis of these toxicogenomic and epigenomic profiles by bioinformatics in the context of phenotypic endpoints, comprises systems biology, which has the potential to comprehensively define the mechanisms by which benzene causes leukemia. We have applied this approach to a molecular epidemiology study of workers exposed to benzene. Hematotoxicity, a significant decrease in almost all blood cell counts, was identified as a phenotypic effect of benzene that occurred even below 1. ppm benzene exposure. We found a significant decrease in the formation of progenitor colonies arising from bone marrow stem cells with increasing benzene exposure, showing that progenitor cells are more sensitive to the effects of benzene than mature blood cells, likely leading to the observed hematotoxicity. Analysis of transcriptomics by microarray in the peripheral blood mononuclear cells of exposed workers, identified genes and pathways (apoptosis, immune response, and inflammatory response) altered at high (>10. ppm) and low (

Original languageEnglish (US)
Pages (from-to)86-93
Number of pages8
JournalChemico-Biological Interactions
Volume184
Issue number1-2
DOIs
StatePublished - Mar 2010
Externally publishedYes

Fingerprint

Systems Biology
Benzene
Genes
Toxicogenetics
Epigenomics
Blood
Blood Cells
Stem Cells
Cells
Gene-Environment Interaction
Molecular Epidemiology
Blood Cell Count
Biomarkers
Microarray Analysis
Bioinformatics
Microarrays
Genomics
Computational Biology
Stem cells
Gene expression

Keywords

  • Benzene
  • Epigenetics
  • Hematotoxicity
  • Human
  • Systems biology
  • Toxicogenomics

ASJC Scopus subject areas

  • Toxicology

Cite this

Zhang, L., McHale, C. M., Rothman, N., Li, G., Ji, Z., Vermeulen, R., ... Lan, Q. (2010). Systems biology of human benzene exposure. Chemico-Biological Interactions, 184(1-2), 86-93. https://doi.org/10.1016/j.cbi.2009.12.011

Systems biology of human benzene exposure. / Zhang, Luoping; McHale, Cliona M.; Rothman, Nathaniel; Li, Guilan; Ji, Zhiying; Vermeulen, Roel; Hubbard, Alan E.; Ren, Xuefeng; Shen, Min; Rappaport, Stephen M.; North, Matthew; Skibola, Christine F.; Yin, Songnian; Vulpe, Christopher; Chanock, Stephen J.; Smith, Martyn T.; Lan, Qing.

In: Chemico-Biological Interactions, Vol. 184, No. 1-2, 03.2010, p. 86-93.

Research output: Contribution to journalArticle

Zhang, L, McHale, CM, Rothman, N, Li, G, Ji, Z, Vermeulen, R, Hubbard, AE, Ren, X, Shen, M, Rappaport, SM, North, M, Skibola, CF, Yin, S, Vulpe, C, Chanock, SJ, Smith, MT & Lan, Q 2010, 'Systems biology of human benzene exposure', Chemico-Biological Interactions, vol. 184, no. 1-2, pp. 86-93. https://doi.org/10.1016/j.cbi.2009.12.011
Zhang L, McHale CM, Rothman N, Li G, Ji Z, Vermeulen R et al. Systems biology of human benzene exposure. Chemico-Biological Interactions. 2010 Mar;184(1-2):86-93. https://doi.org/10.1016/j.cbi.2009.12.011
Zhang, Luoping ; McHale, Cliona M. ; Rothman, Nathaniel ; Li, Guilan ; Ji, Zhiying ; Vermeulen, Roel ; Hubbard, Alan E. ; Ren, Xuefeng ; Shen, Min ; Rappaport, Stephen M. ; North, Matthew ; Skibola, Christine F. ; Yin, Songnian ; Vulpe, Christopher ; Chanock, Stephen J. ; Smith, Martyn T. ; Lan, Qing. / Systems biology of human benzene exposure. In: Chemico-Biological Interactions. 2010 ; Vol. 184, No. 1-2. pp. 86-93.
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