HEMA reduces cell proliferation and induces apoptosis in vitro.
OBJECTIVE
Methacrylate monomers have been identified in aqueous extracts of freshly cured compomers. Both cells in the pulpal cavity and various cells of the oral mucosa can potentially be exposed to these leachables. Short-term exposure to dental monomers at relatively high concentrations induces adverse biological effects in vitro. The mechanisms involved have not been fully elucidated although involvement of various signaling pathways including ROS formation, activation of MAP-kinases and caspases has been suggested. The aim of this study was to investigate potential cellular responses following long-term exposure to relatively low and potentially more clinical relevant HEMA concentrations.


METHODS
A submandibular gland cell line was exposed to HEMA (20-600 microM) for up to 72h. The impact on cell proliferation, apoptosis, and possible underlying mechanisms was assessed by flow cytometry, microscopy and western blotting.


RESULTS
Exposure to HEMA (600 microM) resulted in reduced cell proliferation after 24h and increased apoptosis after 60h. Further, we observed ATM dependent phosphorylation of p53, advocating an initial DNA damage in the HEMA exposed cells.


CONCLUSIONS
In conclusion, we show that exposure to relatively low concentration of HEMA for a prolonged time result in cell death, possibly as a consequence of DNA damage.
Samuelsen
J T
JT
NIOM-Nordic Institute of Dental Materials, N-1305 Haslum, Norway. jts@niom.no
Holme
J A
JA
Becher
R
R
Karlsson
S
S
Morisbak
E
E
Dahl
J E
JE
D000818:Animals; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D020770:Compomers / Q000737:chemistry / Q000633:toxicity*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects; D005434:Flow Cytometry; D008689:Methacrylates / Q000633:toxicity*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D020770:Compomers; D004268:DNA-Binding Proteins; D008689:Methacrylates; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C005044:hydroxyethyl methacrylate; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D053148:Caspase 3