title: Discovery of novel biomarkers by microarray analysis of peripheral blood mononuclear cell gene expression in benzene-exposed workers.
abstract: Benzene is an industrial chemical and component of gasoline that is an established cause of leukemia. To better understand the risk benzene poses, we examined the effect of benzene exposure on peripheral blood mononuclear cell (PBMC) gene expression in a population of shoe-factory workers with well-characterized occupational exposures using microarrays and real-time polymerase chain reaction (PCR). PBMC RNA was stabilized in the field and analyzed using a comprehensive human array, the U133A/B Affymetrix GeneChip set. A matched analysis of six exposed-control pairs was performed. A combination of robust multiarray analysis and ordering of genes using paired t-statistics, along with bootstrapping to control for a 5% familywise error rate, was used to identify differentially expressed genes in a global analysis. This resulted in a set of 29 known genes being identified that were highly likely to be differentially expressed. We also repeated these analyses on a smaller subset of 508 cytokine probe sets and found that the expression of 19 known cytokine genes was significantly different between the exposed and the control subjects. Six genes were selected for confirmation by real-time PCR, and of these, CXCL16, ZNF331, JUN, and PF4 were the most significantly affected by benzene exposure, a finding that was confirmed in a larger data set from 28 subjects. The altered expression was not caused by changes in the makeup of the PBMC fraction. Thus, microarray analysis along with real-time PCR confirmation reveals that altered expressions of CXCL16, ZNF331, JUN, and PF4 are potential biomarkers of benzene exposure.
authors.affiliation: School of Public Health, University of California, Berkeley, California 94720-7360, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Forrest
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Alan E
authors.initials: AE
authors.lastname: Hubbard
authors.forename: Luoping
authors.initials: L
authors.lastname: Zhang
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Guilan
authors.initials: G
authors.lastname: Li
authors.forename: Yen-Ying
authors.initials: YY
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Songnian
authors.initials: S
authors.lastname: Yin
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Smith
mesh_terms: D000328:Adult; D001554:Benzene / Q000633:toxicity*; D015415:Biomarkers; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D002681:China / Q000453:epidemiology; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D016273:Occupational Exposure; D020411:Oligonucleotide Array Sequence Analysis; D010978:Platelet Factor 4 / Q000235:genetics / Q000378:metabolism; D051116:Receptors, Scavenger / Q000096:biosynthesis / Q000235:genetics; D012775:Shoes
chemical_list: D015415:Biomarkers; C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D016207:Cytokines; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D051116:Receptors, Scavenger; C403666:ZNF331 protein, human; D010978:Platelet Factor 4; D001554:Benzene