Induction of DNA double-strand breaks in primary gingival fibroblasts by exposure to dental resin composites.
Dental resin composites and their reactive monomers/co-monomers have been shown to elicit cytotoxic responses in human gingival fibroblasts (HGF), and their metabolic radical intermediates have the potential to attack the DNA backbone, which may induce DNA double-strand breaks (DSBs). In this study we have tested the cytotoxicity and induction of DSBs by the most common composite resin monomers/co-monomers: BisGMA, HEMA, TEGDMA, and UDMA in gingival fibroblasts using the sensitive gamma-H2AX DNA repair focus assay. Our results show increasing monomer cytotoxicities in the order of BisGMA>UDMA>TEGDMA>HEMA, an order that was also observed for their capacity to induce DSBs. BisGMA at the EC50 concentration of 0.09 mm evoked the highest rate of gamma-H2AX foci-formation that was 11-fold higher DNA DSBs as compared to the negative controls that ranged between 0.25 and 0.5gamma-H2AX foci/HGF cell. Our results for the first time show that exposure to dental resin monomers can induce DSBs in primary human oral cavity cells, which underscores their genotoxic capacity.
Urcan
Ebru
E
Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians-University of Munich, Nussbaumstrasse 26, D-80336 Munich, Germany. ebru_urcan@yahoo.com
Scherthan
Harry
H
Styllou
Marianthi
M
Haertel
Uschi
U
Hickel
Reinhard
R
Reichl
Franz-Xaver
FX
D000180:Acrylic Resins / Q000633:toxicity*; D017438:Bisphenol A-Glycidyl Methacrylate / Q000633:toxicity; D002478:Cells, Cultured; D003188:Composite Resins / Q000633:toxicity*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D005881:Gingiva / Q000166:cytology*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008422:Materials Testing; D008689:Methacrylates / Q000633:toxicity; D011092:Polyethylene Glycols / Q000633:toxicity; D011109:Polymethacrylic Acids / Q000633:toxicity; D011140:Polyurethanes / Q000633:toxicity*
D000180:Acrylic Resins; C029012:Composite Dental Resin; D003188:Composite Resins; C468783:H2AX protein, human; D006657:Histones; D008689:Methacrylates; D011109:Polymethacrylic Acids; D011140:Polyurethanes; C029824:urethane dimethacrylate luting resin; C020946:triethylene glycol dimethacrylate; D011092:Polyethylene Glycols; D017438:Bisphenol A-Glycidyl Methacrylate; C005044:hydroxyethyl methacrylate