title: Mono-(2-ethylhexyl) phthalate impairs neurodevelopment: inhibition of proliferation and promotion of differentiation in PC12 cells.
abstract: Di-(2-ethylhexyl)-phthalate (DEHP) is the most widely used plasticizers in daily-life products. In this study we evaluated the influence of mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of DEHP, on the neurodevelopment in vitro. After neuronotypic PC12 cells were exposed to MEHP (0.25, 2.5, 25, and 250 μM), the effects of which on cell proliferation and differentiation were investigated. In undifferentiated PC12 cells, MEHP inhibited cell proliferation in a dose-dependent manner. After 24h of MEHP treatment, there was a dose-dependent G2/M cell cycle arrest as well as a sharp drop of DNA synthesis. During the process of NGF-induced differentiation of the cell line, 4 days of MEHP exposure (2.5-250 μM) increased membrane and cytoskeletal protein contents, enhanced NGF-induced neurite outgrowth, up-regulated the choline acetyl transferase (ChAT) mRNA and down-regulated tyrosine hydroxylase (TH) mRNA levels, which suggested the promoted differentiation towards the acetylcholine (ACh) phenotype at the expense of the dopamine (DA) phenotype. Take together, our results indicate that MEHP has a potential to disturb neurodevelopment by suppressing cell proliferation and promote cell differentiation in neurocytes.
authors.affiliation: Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Chen
authors.forename: Wenjie
authors.initials: W
authors.lastname: Yang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Shunqing
authors.initials: S
authors.lastname: Xu
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000032:analysis; D004247:DNA / Q000096:biosynthesis; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008565:Membrane Proteins / Q000032:analysis; D016501:Neurites / Q000187:drug effects; D018384:Oxidative Stress; D016716:PC12 Cells; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D004247:DNA; D004051:Diethylhexyl Phthalate; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; C016599:mono-(2-ethylhexyl)phthalate