title: Urethane dimethacrylate induces cytotoxicity and regulates cyclooxygenase-2, hemeoxygenase and carboxylesterase expression in human dental pulp cells.
abstract: The toxic effect of urethane dimethacrylate (UDMA), a major dental resin monomer, on human dental pulp is not fully clear. In this study, we investigated the influence of UDMA on the cytotoxicity, cell cycle distribution, apoptosis and related gene expression of dental pulp cells. The role of reactive oxygen species, hemeoxygenase-1 (HO-1) and carboxylesterase (CES) in UDMA cytotoxicity, was evaluated. UDMA induced morphological changes of pulp cells and decreased cell viability by 29-49% at concentrations of 0.1-0.35 mM. UDMA induced G0/G1, G2/M cell cycle arrest and apoptosis. The expression of cdc2, cyclinB1 and cdc25C was inhibited by UDMA. Moreover, UDMA stimulated COX-2, HO-1 and CES2 mRNA expression of pulp cells. The cytotoxicity of UDMA was attenuated by N-acetyl-l-cysteine, catalase and esterase, but was enhanced by Zn-protoporphyrin (HO-1 inhibitor), BNPP (CES inhibitor) and loperamide (CES2 inhibitor). Exposure of UDMA may potentially induce the inflammation and toxicity of dental pulp. These findings are important for understanding the clinical response of human pulp to resin monomers after operative restoration and pulp capping, and also provide clues for improvement of dental materials.
authors.affiliation: Laboratory of Pharmacology, Toxicology & Pulp Biology, Department of Dentistry and School of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan, ROC.
authors.forename: Hsiao-Hua
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Biomedical Science Team, Chang Gung University of Science and Technology, Taoyuan, Taiwan, ROC. Electronic address: mcchang@mail.cgust.edu.tw.
authors.forename: Mei-Chi
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Laboratory of Pharmacology, Toxicology & Pulp Biology, Department of Dentistry and School of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan, ROC.
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Wang
authors.affiliation: Laboratory of Pharmacology, Toxicology & Pulp Biology, Department of Dentistry and School of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan, ROC.
authors.forename: Guay-Fen
authors.initials: GF
authors.lastname: Huang
authors.affiliation: Laboratory of Pharmacology, Toxicology & Pulp Biology, Department of Dentistry and School of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan, ROC.
authors.forename: Yuan-Ling
authors.initials: YL
authors.lastname: Lee
authors.affiliation: Laboratory of Pharmacology, Toxicology & Pulp Biology, Department of Dentistry and School of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan, ROC.
authors.forename: Yin-Lin
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan, ROC.
authors.forename: Chiu-Po
authors.initials: CP
authors.lastname: Chan
authors.affiliation: Biomedical Science Team, Chang Gung University of Science and Technology, Taoyuan, Taiwan, ROC.
authors.forename: Sin-Yuet
authors.initials: SY
authors.lastname: Yeung
authors.affiliation: Laboratory of Pharmacology, Toxicology & Pulp Biology, Department of Dentistry and School of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan, ROC.
authors.forename: Shuei-Kuen
authors.initials: SK
authors.lastname: Tseng
authors.affiliation: Laboratory of Pharmacology, Toxicology & Pulp Biology, Department of Dentistry and School of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan, ROC. Electronic address: jhjeng@ntu.edu.tw.
authors.forename: Jiiang-Huei
authors.initials: JH
authors.lastname: Jeng
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D043182:Carboxylesterase / Q000235:genetics / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008139:Loperamide / Q000494:pharmacology; D008689:Methacrylates / Q000494:pharmacology*; D009596:Nitrophenols / Q000494:pharmacology; D011140:Polyurethanes / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008689:Methacrylates; D009596:Nitrophenols; D011140:Polyurethanes; D011524:Protoporphyrins; D012333:RNA, Messenger; C029824:urethane dimethacrylate luting resin; C017803:zinc protoporphyrin; C002887:bis(4-nitrophenyl)phosphate; D008139:Loperamide; D002374:Catalase; D006419:Heme Oxygenase (Decyclizing); D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D043182:Carboxylesterase; D000111:Acetylcysteine
keywords: Dental pulp; Inflammation; Prostanoids; Resin monomers; Urethane dimethacrylate