title: Phenolic metabolites of benzene inhibited the erythroid differentiation of K562 cells.
abstract: Benzene is a common occupational hazard and a ubiquitous environmental pollutant. Benzene exposure at the levels even below 1ppm still showed hematotoxicity. It is widely accepted that the metabolites of benzene play important roles in the benzene toxicity to the hematopoietic system, but little is known about the effects of benzene metabolites on erythropoiesis. In present study, erythroid progenitor-like K562 cells were used to determine the effects of phenolic metabolites of benzene, including phenol, hydroquinone and 1,2,4-benzenetriol, on the erythroid differentiation. After the treatment with these benzene metabolites at the concentrations with no obvious cytotoxicity, the hemin-induced hemoglobin synthesis in K562 cells decreased in a concentration- and time-dependent manner, and the expression of CD71 and GPA protein on the surface of K562 cells was also inhibited. The reverse transcription-PCR was used to determine the mRNA level of the erythroid related genes in the K562 cells that were treated with benzene metabolites. The hemin-induced expression of globin genes, including α-, β- and γ-globin genes, and the gene encoding the heme synthesis enzyme porphobilinogen deaminase was inhibited by benzene metabolites. When the K562 cells were pretreated with benzene metabolites, the hemin-induced expression of two transcription factor genes GATA-1 and NF-E2 was distinctly reduced, and the pre-treatment with benzene metabolites promoted the decrease of the mRNA level of transcription factor gene GATA-2 by hemin. These results indicated that benzene metabolites inhibited the hemin-induced erythroid differentiation through affecting the transcription of the erythroid related genes.
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Xue
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Qing-Ling
authors.initials: QL
authors.lastname: Han
authors.forename: Zong-Chun
authors.initials: ZC
authors.lastname: Yi
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D001554:Benzene / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects*; D050982:GATA1 Transcription Factor / Q000235:genetics; D050989:GATA2 Transcription Factor / Q000235:genetics; D006021:Glycophorins / Q000032:analysis; D006427:Hemin / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans; D006873:Hydroquinones / Q000737:chemistry / Q000633:toxicity*; D020014:K562 Cells; D019800:Phenol / Q000737:chemistry / Q000633:toxicity*; D011990:Receptors, Transferrin / Q000032:analysis
chemical_list: D015703:Antigens, CD; C068126:CD71 antigen; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050989:GATA2 Transcription Factor; D006021:Glycophorins; D006454:Hemoglobins; D006873:Hydroquinones; D011990:Receptors, Transferrin; C013038:hydroxyhydroquinone; D019800:Phenol; D006427:Hemin; D001554:Benzene; C031927:hydroquinone