title: Identification of human cell responses to benzene and benzene metabolites.
abstract: Benzene is a common air pollutant and confirmed carcinogen, especially in reference to the hematopoietic system. In the present study we analyzed cytokine/chemokine production by, and gene expression induction in, human peripheral blood mononuclear cells upon their exposure to the benzene metabolites catechol, hydroquinone, 1,2,4-benzenetriol, and p-benzoquinone. Protein profiling showed that benzene metabolites can stimulate the production of chemokines, the proinflammatory cytokines TNF-alpha and IL-6, and the Th2 cytokines IL-4 and IL-5. Activated cells showed concurrent suppression of anti-inflammatory cytokine IL-10 expression. We also identified changes in global gene expression patterns in response to benzene metabolite challenges by using high-density oligonucleotide microarrays. Treatment with 1,2,4-benzenetriol resulted in the suppression of genes related to the regulation of protein expression and a concomitant activation of genes that encode heat shock proteins and cytochrome P450 family members. Protein and gene expression profiling identified unique human cellular responses upon exposure to benzene and benzene metabolites.
authors.affiliation: Department of Medicine, University of Illinois, Chicago, IL 60612, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Gillis
authors.forename: Igor M
authors.initials: IM
authors.lastname: Gavin
authors.forename: Zarema
authors.initials: Z
authors.lastname: Arbieva
authors.forename: Stephen T
authors.initials: ST
authors.lastname: King
authors.forename: Sundararajan
authors.initials: S
authors.lastname: Jayaraman
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabhakar
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry; D001554:Benzene / Q000378:metabolism* / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry; D002396:Catechols / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D006873:Hydroquinones / Q000737:chemistry; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D012313:RNA / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016227:Benzoquinones; D002396:Catechols; D016207:Cytokines; D006873:Hydroquinones; D016753:Interleukin-10; C013038:hydroxyhydroquinone; C004532:quinone; D012313:RNA; D001554:Benzene; C034221:catechol; C031927:hydroquinone