title: Global gene expression profiling of a population exposed to a range of benzene levels.
abstract: BACKGROUND
  Benzene, an established cause of acute myeloid leukemia (AML), may also cause one or more lymphoid malignancies in humans. Previously, we identified genes and pathways associated with exposure to high (> 10 ppm) levels of benzene through transcriptomic analyses of blood cells from a small number of occupationally exposed workers.
  
  
  OBJECTIVE
  The goals of this study were to identify potential biomarkers of benzene exposure and/or early effects and to elucidate mechanisms relevant to risk of hematotoxicity, leukemia, and lymphoid malignancy in occupationally exposed individuals, many of whom were exposed to benzene levels < 1 ppm, the current U.S. occupational standard.
  
  
  METHODS
  We analyzed global gene expression in the peripheral blood mononuclear cells of 125 workers exposed to benzene levels ranging from < 1 ppm to > 10 ppm. Study design and analysis with a mixed-effects model minimized potential confounding and experimental variability.
  
  
  RESULTS
  We observed highly significant widespread perturbation of gene expression at all exposure levels. The AML pathway was among the pathways most significantly associated with benzene exposure. Immune response pathways were associated with most exposure levels, potentially providing biological plausibility for an association between lymphoma and benzene exposure. We identified a 16-gene expression signature associated with all levels of benzene exposure.
  
  
  CONCLUSIONS
  Our findings suggest that chronic benzene exposure, even at levels below the current U.S. occupational standard, perturbs many genes, biological processes, and pathways. These findings expand our understanding of the mechanisms by which benzene may induce hematotoxicity, leukemia, and lymphoma and reveal relevant potential biomarkers associated with a range of exposures.
authors.affiliation: School of Public Health, University of California-Berkeley, Berkeley, California 64720, USA. cmchale@berkeley.edu
authors.forename: Cliona M
authors.initials: CM
authors.lastname: McHale
authors.forename: Luoping
authors.initials: L
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
authors.forename: Guilan
authors.initials: G
authors.lastname: Li
authors.forename: Alan E
authors.initials: AE
authors.lastname: Hubbard
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Porter
authors.forename: Reuben
authors.initials: R
authors.lastname: Thomas
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Portier
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Rappaport
authors.forename: Songnian
authors.initials: S
authors.lastname: Yin
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Smith
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
mesh_terms: D000328:Adult; D001554:Benzene / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007938:Leukemia / Q000139:chemically induced; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008223:Lymphoma / Q000139:chemically induced; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects; D055815:Young Adult
chemical_list: D001554:Benzene