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Ethylene glycol dimethacrylate and diethylene glycol dimethacrylate exhibits cytotoxic and genotoxic effect on human gingival fibroblasts via induction of reactive oxygen species.

Identifieur interne : 000087 ( Main/Exploration ); précédent : 000086; suivant : 000088

Ethylene glycol dimethacrylate and diethylene glycol dimethacrylate exhibits cytotoxic and genotoxic effect on human gingival fibroblasts via induction of reactive oxygen species.

Auteurs : Anna Bielecka-Kowalska [Pologne] ; Piotr Czarny [Pologne] ; Paulina Wigner [Pologne] ; Ewelina Synowiec [Pologne] ; Bartosz Kowalski [Pologne] ; Marzena Szwed [Pologne] ; Renata Krupa [Pologne] ; Monika Toma [Pologne] ; Malgorzata Drzewiecka [Pologne] ; Ireneusz Majsterek [Pologne] ; Janusz Szemraj [Pologne] ; Tomasz Sliwinski [Pologne] ; Michał Kowalski [Pologne]

Source :

RBID : pubmed:29107684

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English descriptors

Abstract

Although methacrylic acid derivatives in their polymeric form are considered to be safe, insufficient polymerization and the release of monomers due to either mechanical or enzymatical factors can lead to their reaching millimolar concentrations in local tissue. The present study evaluates the effect of two methacrylate monomers - ethylene glycol dimethacrylate (EGDMA) and diethylene glycol dimethacrylate (DEGDMA) - on human gingival fibroblasts (HGFs). Both monomers were found to reduce cells viability in MTT assay, increase apoptosis and cause cell cycle arrest in G1/G0 phase. They also increased intracellular reactive oxygen species (ROS) production as measured by DCFH-DA and DHE probes and increased expression of GPx4 and SOD2. Both monomers increased DNA damage in comet assay. Moreover, HGFs were not able to repair those lesions within 120min of repair incubation. However, the monomers were not found to have any effect on the integrity of isolated plasmids. We postulate that EGDMA and DEGDMA exhibit their cytotoxic and genotoxic properties via increased production of ROS, which cause DNA damage, affect apoptosis, viability and cell cycle. Further studies are needed to better understand the properties of methacrylic acid monomers and to evaluate the risk that they cause for patients, dentists and dental technicians.

DOI: 10.1016/j.tiv.2017.10.028
PubMed: 29107684


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<name sortKey="Wigner, Paulina" sort="Wigner, Paulina" uniqKey="Wigner P" first="Paulina" last="Wigner">Paulina Wigner</name>
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<name sortKey="Drzewiecka, Malgorzata" sort="Drzewiecka, Malgorzata" uniqKey="Drzewiecka M" first="Malgorzata" last="Drzewiecka">Malgorzata Drzewiecka</name>
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<term>Apoptosis (drug effects)</term>
<term>Cell Survival (drug effects)</term>
<term>Cells, Cultured (MeSH)</term>
<term>Comet Assay (MeSH)</term>
<term>Cross-Linking Reagents (toxicity)</term>
<term>DNA Damage (MeSH)</term>
<term>DNA Repair (drug effects)</term>
<term>Dental Materials (toxicity)</term>
<term>Enzyme Induction (drug effects)</term>
<term>Ethylene Glycols (toxicity)</term>
<term>G1 Phase (drug effects)</term>
<term>Gingiva (cytology)</term>
<term>Gingiva (drug effects)</term>
<term>Gingiva (metabolism)</term>
<term>Glutathione Peroxidase (chemistry)</term>
<term>Glutathione Peroxidase (genetics)</term>
<term>Glutathione Peroxidase (metabolism)</term>
<term>Humans (MeSH)</term>
<term>Methacrylates (toxicity)</term>
<term>Osmolar Concentration (MeSH)</term>
<term>Oxidative Stress (drug effects)</term>
<term>Phospholipid Hydroperoxide Glutathione Peroxidase (MeSH)</term>
<term>Plasmids (drug effects)</term>
<term>Reactive Oxygen Species (agonists)</term>
<term>Reactive Oxygen Species (metabolism)</term>
<term>Superoxide Dismutase (chemistry)</term>
<term>Superoxide Dismutase (genetics)</term>
<term>Superoxide Dismutase (metabolism)</term>
</keywords>
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<term>Altération de l'ADN (MeSH)</term>
<term>Apoptose (effets des médicaments et des substances chimiques)</term>
<term>Cellules cultivées (MeSH)</term>
<term>Concentration osmolaire (MeSH)</term>
<term>Espèces réactives de l'oxygène (agonistes)</term>
<term>Espèces réactives de l'oxygène (métabolisme)</term>
<term>Gencive (cytologie)</term>
<term>Gencive (effets des médicaments et des substances chimiques)</term>
<term>Gencive (métabolisme)</term>
<term>Glutathione peroxidase (composition chimique)</term>
<term>Glutathione peroxidase (génétique)</term>
<term>Glutathione peroxidase (métabolisme)</term>
<term>Humains (MeSH)</term>
<term>Induction enzymatique (effets des médicaments et des substances chimiques)</term>
<term>Matériaux dentaires (toxicité)</term>
<term>Méthacrylates (toxicité)</term>
<term>Phase G1 (effets des médicaments et des substances chimiques)</term>
<term>Plasmides (effets des médicaments et des substances chimiques)</term>
<term>Réactifs réticulants (toxicité)</term>
<term>Réparation de l'ADN (effets des médicaments et des substances chimiques)</term>
<term>Stress oxydatif (effets des médicaments et des substances chimiques)</term>
<term>Superoxide dismutase (composition chimique)</term>
<term>Superoxide dismutase (génétique)</term>
<term>Superoxide dismutase (métabolisme)</term>
<term>Survie cellulaire (effets des médicaments et des substances chimiques)</term>
<term>Test des comètes (MeSH)</term>
<term>Éthylène glycols (toxicité)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="agonists" xml:lang="en">
<term>Reactive Oxygen Species</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Glutathione Peroxidase</term>
<term>Superoxide Dismutase</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Glutathione Peroxidase</term>
<term>Superoxide Dismutase</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Glutathione Peroxidase</term>
<term>Reactive Oxygen Species</term>
<term>Superoxide Dismutase</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en">
<term>Cross-Linking Reagents</term>
<term>Dental Materials</term>
<term>Ethylene Glycols</term>
<term>Methacrylates</term>
</keywords>
<keywords scheme="MESH" qualifier="agonistes" xml:lang="fr">
<term>Espèces réactives de l'oxygène</term>
</keywords>
<keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr">
<term>Glutathione peroxidase</term>
<term>Superoxide dismutase</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr">
<term>Gencive</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en">
<term>Gingiva</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en">
<term>Apoptosis</term>
<term>Cell Survival</term>
<term>DNA Repair</term>
<term>Enzyme Induction</term>
<term>G1 Phase</term>
<term>Gingiva</term>
<term>Oxidative Stress</term>
<term>Plasmids</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr">
<term>Apoptose</term>
<term>Gencive</term>
<term>Induction enzymatique</term>
<term>Phase G1</term>
<term>Plasmides</term>
<term>Réparation de l'ADN</term>
<term>Stress oxydatif</term>
<term>Survie cellulaire</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Glutathione peroxidase</term>
<term>Superoxide dismutase</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Gingiva</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Espèces réactives de l'oxygène</term>
<term>Gencive</term>
<term>Glutathione peroxidase</term>
<term>Superoxide dismutase</term>
</keywords>
<keywords scheme="MESH" qualifier="toxicité" xml:lang="fr">
<term>Matériaux dentaires</term>
<term>Méthacrylates</term>
<term>Réactifs réticulants</term>
<term>Éthylène glycols</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Cells, Cultured</term>
<term>Comet Assay</term>
<term>DNA Damage</term>
<term>Humans</term>
<term>Osmolar Concentration</term>
<term>Phospholipid Hydroperoxide Glutathione Peroxidase</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Altération de l'ADN</term>
<term>Cellules cultivées</term>
<term>Concentration osmolaire</term>
<term>Humains</term>
<term>Test des comètes</term>
</keywords>
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<front>
<div type="abstract" xml:lang="en">Although methacrylic acid derivatives in their polymeric form are considered to be safe, insufficient polymerization and the release of monomers due to either mechanical or enzymatical factors can lead to their reaching millimolar concentrations in local tissue. The present study evaluates the effect of two methacrylate monomers - ethylene glycol dimethacrylate (EGDMA) and diethylene glycol dimethacrylate (DEGDMA) - on human gingival fibroblasts (HGFs). Both monomers were found to reduce cells viability in MTT assay, increase apoptosis and cause cell cycle arrest in G1/G0 phase. They also increased intracellular reactive oxygen species (ROS) production as measured by DCFH-DA and DHE probes and increased expression of GPx4 and SOD2. Both monomers increased DNA damage in comet assay. Moreover, HGFs were not able to repair those lesions within 120min of repair incubation. However, the monomers were not found to have any effect on the integrity of isolated plasmids. We postulate that EGDMA and DEGDMA exhibit their cytotoxic and genotoxic properties via increased production of ROS, which cause DNA damage, affect apoptosis, viability and cell cycle. Further studies are needed to better understand the properties of methacrylic acid monomers and to evaluate the risk that they cause for patients, dentists and dental technicians.</div>
</front>
</TEI>
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<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">29107684</PMID>
<DateCompleted>
<Year>2018</Year>
<Month>09</Month>
<Day>18</Day>
</DateCompleted>
<DateRevised>
<Year>2019</Year>
<Month>12</Month>
<Day>10</Day>
</DateRevised>
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<Journal>
<ISSN IssnType="Electronic">1879-3177</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>47</Volume>
<PubDate>
<Year>2018</Year>
<Month>Mar</Month>
</PubDate>
</JournalIssue>
<Title>Toxicology in vitro : an international journal published in association with BIBRA</Title>
<ISOAbbreviation>Toxicol In Vitro</ISOAbbreviation>
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<ArticleTitle>Ethylene glycol dimethacrylate and diethylene glycol dimethacrylate exhibits cytotoxic and genotoxic effect on human gingival fibroblasts via induction of reactive oxygen species.</ArticleTitle>
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<MedlinePgn>8-17</MedlinePgn>
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<Abstract>
<AbstractText>Although methacrylic acid derivatives in their polymeric form are considered to be safe, insufficient polymerization and the release of monomers due to either mechanical or enzymatical factors can lead to their reaching millimolar concentrations in local tissue. The present study evaluates the effect of two methacrylate monomers - ethylene glycol dimethacrylate (EGDMA) and diethylene glycol dimethacrylate (DEGDMA) - on human gingival fibroblasts (HGFs). Both monomers were found to reduce cells viability in MTT assay, increase apoptosis and cause cell cycle arrest in G1/G0 phase. They also increased intracellular reactive oxygen species (ROS) production as measured by DCFH-DA and DHE probes and increased expression of GPx4 and SOD2. Both monomers increased DNA damage in comet assay. Moreover, HGFs were not able to repair those lesions within 120min of repair incubation. However, the monomers were not found to have any effect on the integrity of isolated plasmids. We postulate that EGDMA and DEGDMA exhibit their cytotoxic and genotoxic properties via increased production of ROS, which cause DNA damage, affect apoptosis, viability and cell cycle. Further studies are needed to better understand the properties of methacrylic acid monomers and to evaluate the risk that they cause for patients, dentists and dental technicians.</AbstractText>
<CopyrightInformation>Copyright © 2017 Elsevier Ltd. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Bielecka-Kowalska</LastName>
<ForeName>Anna</ForeName>
<Initials>A</Initials>
<AffiliationInfo>
<Affiliation>Non-public Medical Center "Akoria", Lodz, Poland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Czarny</LastName>
<ForeName>Piotr</ForeName>
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<AffiliationInfo>
<Affiliation>Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Wigner</LastName>
<ForeName>Paulina</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.</Affiliation>
</AffiliationInfo>
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<ForeName>Ewelina</ForeName>
<Initials>E</Initials>
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<Affiliation>Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.</Affiliation>
</AffiliationInfo>
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<LastName>Kowalski</LastName>
<ForeName>Bartosz</ForeName>
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<Affiliation>Department of Maxillofacial Surgery, Medical University of Lodz, Lodz, Poland.</Affiliation>
</AffiliationInfo>
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<LastName>Szwed</LastName>
<ForeName>Marzena</ForeName>
<Initials>M</Initials>
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<Affiliation>Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Krupa</LastName>
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<Affiliation>Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.</Affiliation>
</AffiliationInfo>
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<Initials>I</Initials>
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<Affiliation>Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, Poland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Szemraj</LastName>
<ForeName>Janusz</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Sliwinski</LastName>
<ForeName>Tomasz</ForeName>
<Initials>T</Initials>
<AffiliationInfo>
<Affiliation>Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland. Electronic address: tomsliw@biol.uni.lodz.pl.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Kowalski</LastName>
<ForeName>Michał</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
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<Language>eng</Language>
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<PublicationType UI="D003160">Comparative Study</PublicationType>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2017</Year>
<Month>10</Month>
<Day>28</Day>
</ArticleDate>
</Article>
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<Country>England</Country>
<MedlineTA>Toxicol In Vitro</MedlineTA>
<NlmUniqueID>8712158</NlmUniqueID>
<ISSNLinking>0887-2333</ISSNLinking>
</MedlineJournalInfo>
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<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D003432">Cross-Linking Reagents</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D003764">Dental Materials</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D005026">Ethylene Glycols</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D008689">Methacrylates</NameOfSubstance>
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<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D017382">Reactive Oxygen Species</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>2358-84-1</RegistryNumber>
<NameOfSubstance UI="C047521">diethylene glycol dimethacrylate monomer</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>7BK5G69305</RegistryNumber>
<NameOfSubstance UI="C004919">ethylene dimethacrylate</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 1.11.1.12</RegistryNumber>
<NameOfSubstance UI="D000080662">Phospholipid Hydroperoxide Glutathione Peroxidase</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 1.11.1.9</RegistryNumber>
<NameOfSubstance UI="D005979">Glutathione Peroxidase</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 1.15.1.1</RegistryNumber>
<NameOfSubstance UI="D013482">Superoxide Dismutase</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 1.15.1.1</RegistryNumber>
<NameOfSubstance UI="C431683">superoxide dismutase 2</NameOfSubstance>
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<CitationSubset>IM</CitationSubset>
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<MeshHeading>
<DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
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<MeshHeading>
<DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName>
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<DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D004249" MajorTopicYN="N">DNA Damage</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D004260" MajorTopicYN="N">DNA Repair</DescriptorName>
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<MeshHeading>
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</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004790" MajorTopicYN="N">Enzyme Induction</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D005026" MajorTopicYN="N">Ethylene Glycols</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D016193" MajorTopicYN="N">G1 Phase</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D005881" MajorTopicYN="N">Gingiva</DescriptorName>
<QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
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<MeshHeading>
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<Keyword MajorTopicYN="N">DNA damage</Keyword>
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