title: Evaluation of toxicological biomarkers in secreted proteins of HepG2 cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and their expressions in the plasma of rats and incineration workers.
abstract: Toxicological biomarkers of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) were investigated in proteins secreted by HepG2 cells and their expression levels were determined in the plasma of rats exposed to 2,3,7,8-TCDD and in the plasma of incineration workers exposed to dioxins. HepG2 cells were treated with various concentrations of 2,3,7,8-TCDD (0, 0.25, 0.5, 1, 2.5, 5, 10, 25 nM) for 24 or 48 h. MTT and Comet assays were performed to determine cytotoxicities and genotoxicities to select exposure concentrations for the proteomic analysis of proteins secreted by 2,3,7,8-TCDD-treated cells. In the proteomic analysis, dose- and time-dependent toxicological biomarkers were evaluated using two pI ranges (4-7 and 6-9) using a large gel 2-DE system. Fifteen secreted proteins were identified by a nano-LC-ESI-MS/MS and nano-ESI on a Q-TOF2 MS and the identities of eight secreted proteins including glyoxalase 1 (GLO 1), homogentisate dioxygenase (HGD), peroxiredoxin 1 (PRX 1), proteasome subunit beta type (PSMB) 5 and 6, UDP-glucose 6-dehydrogenase (UDP-GlcDH), hydroxyacyl-coenzyme A dehydrogenase (HADH) and serotransferrin (STF) were confirmed by western blotting. Of these, PSMB 5 and PRX 1 were also found in the plasma of rats exposed to 2,3,7,8-TCDD, whereas GLO 1, HGD, PSMB 6 and PRX 1 were found in the plasma of incineration workers exposed to dioxins.
authors.affiliation: Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea.
authors.forename: Sohee
authors.initials: S
authors.lastname: Phark
authors.affiliation: Pharmacognosy Lab., College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: School of Environmental Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea.
authors.forename: Seonyoung
authors.initials: S
authors.lastname: Choi
authors.affiliation: Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea.
authors.forename: Ji-youn
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea.
authors.forename: Yoonjin
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Metabolome Analysis Team, Korea Basic Science Institute, Seoul 136-713, Republic of Korea.
authors.forename: Jong Bok
authors.initials: JB
authors.lastname: Seo
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Science, Cheongju University, Cheongju 360-764, Republic of Korea.
authors.forename: Woon-Won
authors.initials: WW
authors.lastname: Jung
authors.affiliation: Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea. Electronic address: dsul@korea.ac.kr.
authors.forename: Donggeun
authors.initials: D
authors.lastname: Sul
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000235:genetics; D040901:Proteomics; D051381:Rats
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D000072317:Polychlorinated Dibenzodioxins
keywords: 2,3,7,8-TCDD; 2-D gel electrophoresis; Biomarkers; Dioxins; HepG2; Incineration; Plasma; Secreted proteins