Cytotoxicity and genotoxicity of nano - and microparticulate copper oxide: role of solubility and intracellular bioavailability
Nano- or microscale copper oxide particles (CuO NP, CuO MP) are increasingly applied as catalysts or antimicrobial additives. This increases the risk of adverse health effects, since copper ions are cytotoxic under overload conditions. The extra- and intracellular bioavailability of CuO NP and CuO M...
Gespeichert in:
| Veröffentlicht in: | Particle and fibre toxicology 2014-02, Vol.11 (1), p.10-10, Article 10 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 10 |
|---|---|
| container_issue | 1 |
| container_start_page | 10 |
| container_title | Particle and fibre toxicology |
| container_volume | 11 |
| creator | Semisch, Annetta Ohle, Julia Witt, Barbara Hartwig, Andrea |
| description | Nano- or microscale copper oxide particles (CuO NP, CuO MP) are increasingly applied as catalysts or antimicrobial additives. This increases the risk of adverse health effects, since copper ions are cytotoxic under overload conditions.
The extra- and intracellular bioavailability of CuO NP and CuO MP were explored. In addition, different endpoints related to cytotoxicity as well as direct and indirect genotoxicity of the copper oxides and copper chloride (CuCl2) were compared.
Comprehensively characterized CuO NP and CuO MP were analysed regarding their copper ion release in model fluids. In all media investigated, CuO NP released far more copper ions than CuO MP, with most pronounced dissolution in artificial lysosomal fluid. CuO NP and CuCl2 caused a pronounced and dose dependent decrease of colony forming ability (CFA) in A549 and HeLa S3 cells, whereas CuO MP exerted no cytotoxicity at concentrations up to 50 μg/mL. Cell death induced by CuO NP was at least in part due to apoptosis, as determined by subdiploid DNA as well as via translocation of the apoptosis inducing factor (AIF) into the cell nucleus. Similarly, only CuO NP induced significant amounts of DNA strand breaks in HeLa S3 cells, whereas all three compounds elevated the level of H2O2-induced DNA strand breaks. Finally, all copper compounds diminished the H2O2-induced poly(ADP-ribosyl)ation, catalysed predominantly by poly(ADP-ribose)polymerase-1 (PARP-1); here, again, CuO NP exerted the strongest effect. Copper derived from CuO NP, CuO MP and CuCl2 accumulated in the soluble cytoplasmic and nuclear fractions of A549 cells, yielding similar concentrations in the cytoplasm but highest concentrations in the nucleus in case of CuO NP.
The results support the high cytotoxicity of CuO NP and CuCl2 and the missing cytotoxicity of CuO MP under the conditions applied. For these differences in cytotoxicity, extracellular copper ion levels due to dissolution of particles as well as differences in physicochemical properties of the particles like surface area may be of major relevance. Regarding direct and indirect genotoxicity, especially the high copper content in the cell nucleus derived after cell treatment with CuO NP appears to be decisive. |
| doi_str_mv | 10.1186/1743-8977-11-10 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3943586</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A539684067</galeid><sourcerecordid>A539684067</sourcerecordid><originalsourceid>FETCH-LOGICAL-b680t-176951851f6145bfe2779a7f0512caee7f01e1de08745de01bc89b33abeab0c3</originalsourceid><addsrcrecordid>eNp1kkFv1DAQhSNERUvhzA1F4gKHtJ44iRMOlcoKaKVKlaB3y3EmiyvHDrZTdU_8dRy23TZVkQ9jzXzzNH6eJHkH5Aigro6BFTSrG8YygAzIi-Rgl3n56L6fvPb-mhBa1iW8SvbzosxJ05CD5M9qE2ywt0qqsEmF6dI1moeE7VMjjE2zf6VBSWdH4YKSkxYBU2nHEV0a6Q4_p85qnDu81VOr9L2gMsEJiVrHHpe2yoobobTYEm-SvV5oj2_v4mFy9e3r1eosu7j8fr46vcjaqiYhA1Y1JcTh-wqKsu0xZ6wRrCcl5FIgxhsgdEhqVpQxQCvrpqVUtChaIulhcrKVHad2wE7iPJPmo1ODcBtuheLLilG_-NrecNoU0bQqCnzZCsT5_yOwrEg78Nl_PvvPATiQKPLxbgpnf0_oAx-Un50RBu3kOcTXUJozChH98AS9tpMz0aJIkaJiRU2KB2otNHJlejtbPYvy05I2VV2QikXq6Bkqng7jj1qDvYr5RcOnRUNkAt6GtZi85-c_fyzZ4y0bV8N7h_3OEyB83tFnXHj_-C92_P1S0r8N-eNw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1504674804</pqid></control><display><type>article</type><title>Cytotoxicity and genotoxicity of nano - and microparticulate copper oxide: role of solubility and intracellular bioavailability</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>SpringerLink Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>Springer Nature OA Free Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Semisch, Annetta ; Ohle, Julia ; Witt, Barbara ; Hartwig, Andrea</creator><creatorcontrib>Semisch, Annetta ; Ohle, Julia ; Witt, Barbara ; Hartwig, Andrea</creatorcontrib><description>Nano- or microscale copper oxide particles (CuO NP, CuO MP) are increasingly applied as catalysts or antimicrobial additives. This increases the risk of adverse health effects, since copper ions are cytotoxic under overload conditions.
The extra- and intracellular bioavailability of CuO NP and CuO MP were explored. In addition, different endpoints related to cytotoxicity as well as direct and indirect genotoxicity of the copper oxides and copper chloride (CuCl2) were compared.
Comprehensively characterized CuO NP and CuO MP were analysed regarding their copper ion release in model fluids. In all media investigated, CuO NP released far more copper ions than CuO MP, with most pronounced dissolution in artificial lysosomal fluid. CuO NP and CuCl2 caused a pronounced and dose dependent decrease of colony forming ability (CFA) in A549 and HeLa S3 cells, whereas CuO MP exerted no cytotoxicity at concentrations up to 50 μg/mL. Cell death induced by CuO NP was at least in part due to apoptosis, as determined by subdiploid DNA as well as via translocation of the apoptosis inducing factor (AIF) into the cell nucleus. Similarly, only CuO NP induced significant amounts of DNA strand breaks in HeLa S3 cells, whereas all three compounds elevated the level of H2O2-induced DNA strand breaks. Finally, all copper compounds diminished the H2O2-induced poly(ADP-ribosyl)ation, catalysed predominantly by poly(ADP-ribose)polymerase-1 (PARP-1); here, again, CuO NP exerted the strongest effect. Copper derived from CuO NP, CuO MP and CuCl2 accumulated in the soluble cytoplasmic and nuclear fractions of A549 cells, yielding similar concentrations in the cytoplasm but highest concentrations in the nucleus in case of CuO NP.
The results support the high cytotoxicity of CuO NP and CuCl2 and the missing cytotoxicity of CuO MP under the conditions applied. For these differences in cytotoxicity, extracellular copper ion levels due to dissolution of particles as well as differences in physicochemical properties of the particles like surface area may be of major relevance. Regarding direct and indirect genotoxicity, especially the high copper content in the cell nucleus derived after cell treatment with CuO NP appears to be decisive.</description><identifier>ISSN: 1743-8977</identifier><identifier>EISSN: 1743-8977</identifier><identifier>DOI: 10.1186/1743-8977-11-10</identifier><identifier>PMID: 24520990</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Analysis ; Apoptosis ; Apoptosis - drug effects ; Atoms & subatomic particles ; Bioavailability ; Biological Availability ; Caspase 3 - metabolism ; Caspase 7 - metabolism ; Cell death ; Cell Nucleus - metabolism ; Cell Survival - drug effects ; Copper - chemistry ; Copper - pharmacokinetics ; Copper - toxicity ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; DNA Damage ; Endotoxins - analysis ; Enzymes ; Fluids ; Health aspects ; HeLa Cells ; Humans ; Indicators and Reagents ; Life sciences ; Mass spectrometry ; Metal Nanoparticles - toxicity ; Micronucleus Tests ; Microscopy, Electron, Scanning ; Mutagens ; Nanoparticles ; Particle Size ; Political aspects ; Poly Adenosine Diphosphate Ribose - metabolism ; Proteins ; Scanning electron microscopy ; Software ; Solubility ; Translocation, Genetic ; Transmission electron microscopy ; Variance analysis ; Viscosity</subject><ispartof>Particle and fibre toxicology, 2014-02, Vol.11 (1), p.10-10, Article 10</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Semisch et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2014 Semisch et al.; licensee BioMed Central Ltd. 2014 Semisch et al.; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b680t-176951851f6145bfe2779a7f0512caee7f01e1de08745de01bc89b33abeab0c3</citedby><cites>FETCH-LOGICAL-b680t-176951851f6145bfe2779a7f0512caee7f01e1de08745de01bc89b33abeab0c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943586/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943586/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24520990$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Semisch, Annetta</creatorcontrib><creatorcontrib>Ohle, Julia</creatorcontrib><creatorcontrib>Witt, Barbara</creatorcontrib><creatorcontrib>Hartwig, Andrea</creatorcontrib><title>Cytotoxicity and genotoxicity of nano - and microparticulate copper oxide: role of solubility and intracellular bioavailability</title><title>Particle and fibre toxicology</title><addtitle>Part Fibre Toxicol</addtitle><description>Nano- or microscale copper oxide particles (CuO NP, CuO MP) are increasingly applied as catalysts or antimicrobial additives. This increases the risk of adverse health effects, since copper ions are cytotoxic under overload conditions.
The extra- and intracellular bioavailability of CuO NP and CuO MP were explored. In addition, different endpoints related to cytotoxicity as well as direct and indirect genotoxicity of the copper oxides and copper chloride (CuCl2) were compared.
Comprehensively characterized CuO NP and CuO MP were analysed regarding their copper ion release in model fluids. In all media investigated, CuO NP released far more copper ions than CuO MP, with most pronounced dissolution in artificial lysosomal fluid. CuO NP and CuCl2 caused a pronounced and dose dependent decrease of colony forming ability (CFA) in A549 and HeLa S3 cells, whereas CuO MP exerted no cytotoxicity at concentrations up to 50 μg/mL. Cell death induced by CuO NP was at least in part due to apoptosis, as determined by subdiploid DNA as well as via translocation of the apoptosis inducing factor (AIF) into the cell nucleus. Similarly, only CuO NP induced significant amounts of DNA strand breaks in HeLa S3 cells, whereas all three compounds elevated the level of H2O2-induced DNA strand breaks. Finally, all copper compounds diminished the H2O2-induced poly(ADP-ribosyl)ation, catalysed predominantly by poly(ADP-ribose)polymerase-1 (PARP-1); here, again, CuO NP exerted the strongest effect. Copper derived from CuO NP, CuO MP and CuCl2 accumulated in the soluble cytoplasmic and nuclear fractions of A549 cells, yielding similar concentrations in the cytoplasm but highest concentrations in the nucleus in case of CuO NP.
The results support the high cytotoxicity of CuO NP and CuCl2 and the missing cytotoxicity of CuO MP under the conditions applied. For these differences in cytotoxicity, extracellular copper ion levels due to dissolution of particles as well as differences in physicochemical properties of the particles like surface area may be of major relevance. Regarding direct and indirect genotoxicity, especially the high copper content in the cell nucleus derived after cell treatment with CuO NP appears to be decisive.</description><subject>Analysis</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Atoms & subatomic particles</subject><subject>Bioavailability</subject><subject>Biological Availability</subject><subject>Caspase 3 - metabolism</subject><subject>Caspase 7 - metabolism</subject><subject>Cell death</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Survival - drug effects</subject><subject>Copper - chemistry</subject><subject>Copper - pharmacokinetics</subject><subject>Copper - toxicity</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>Endotoxins - analysis</subject><subject>Enzymes</subject><subject>Fluids</subject><subject>Health aspects</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Indicators and Reagents</subject><subject>Life sciences</subject><subject>Mass spectrometry</subject><subject>Metal Nanoparticles - toxicity</subject><subject>Micronucleus Tests</subject><subject>Microscopy, Electron, Scanning</subject><subject>Mutagens</subject><subject>Nanoparticles</subject><subject>Particle Size</subject><subject>Political aspects</subject><subject>Poly Adenosine Diphosphate Ribose - metabolism</subject><subject>Proteins</subject><subject>Scanning electron microscopy</subject><subject>Software</subject><subject>Solubility</subject><subject>Translocation, Genetic</subject><subject>Transmission electron microscopy</subject><subject>Variance analysis</subject><subject>Viscosity</subject><issn>1743-8977</issn><issn>1743-8977</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kkFv1DAQhSNERUvhzA1F4gKHtJ44iRMOlcoKaKVKlaB3y3EmiyvHDrZTdU_8dRy23TZVkQ9jzXzzNH6eJHkH5Aigro6BFTSrG8YygAzIi-Rgl3n56L6fvPb-mhBa1iW8SvbzosxJ05CD5M9qE2ywt0qqsEmF6dI1moeE7VMjjE2zf6VBSWdH4YKSkxYBU2nHEV0a6Q4_p85qnDu81VOr9L2gMsEJiVrHHpe2yoobobTYEm-SvV5oj2_v4mFy9e3r1eosu7j8fr46vcjaqiYhA1Y1JcTh-wqKsu0xZ6wRrCcl5FIgxhsgdEhqVpQxQCvrpqVUtChaIulhcrKVHad2wE7iPJPmo1ODcBtuheLLilG_-NrecNoU0bQqCnzZCsT5_yOwrEg78Nl_PvvPATiQKPLxbgpnf0_oAx-Un50RBu3kOcTXUJozChH98AS9tpMz0aJIkaJiRU2KB2otNHJlejtbPYvy05I2VV2QikXq6Bkqng7jj1qDvYr5RcOnRUNkAt6GtZi85-c_fyzZ4y0bV8N7h_3OEyB83tFnXHj_-C92_P1S0r8N-eNw</recordid><startdate>20140213</startdate><enddate>20140213</enddate><creator>Semisch, Annetta</creator><creator>Ohle, Julia</creator><creator>Witt, Barbara</creator><creator>Hartwig, Andrea</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7SR</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>K9.</scope><scope>KB.</scope><scope>KR7</scope><scope>L6V</scope><scope>M0S</scope><scope>M1P</scope><scope>M7S</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>5PM</scope></search><sort><creationdate>20140213</creationdate><title>Cytotoxicity and genotoxicity of nano - and microparticulate copper oxide: role of solubility and intracellular bioavailability</title><author>Semisch, Annetta ; Ohle, Julia ; Witt, Barbara ; Hartwig, Andrea</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b680t-176951851f6145bfe2779a7f0512caee7f01e1de08745de01bc89b33abeab0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Analysis</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Atoms & subatomic particles</topic><topic>Bioavailability</topic><topic>Biological Availability</topic><topic>Caspase 3 - metabolism</topic><topic>Caspase 7 - metabolism</topic><topic>Cell death</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Survival - drug effects</topic><topic>Copper - chemistry</topic><topic>Copper - pharmacokinetics</topic><topic>Copper - toxicity</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Damage</topic><topic>Endotoxins - analysis</topic><topic>Enzymes</topic><topic>Fluids</topic><topic>Health aspects</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Indicators and Reagents</topic><topic>Life sciences</topic><topic>Mass spectrometry</topic><topic>Metal Nanoparticles - toxicity</topic><topic>Micronucleus Tests</topic><topic>Microscopy, Electron, Scanning</topic><topic>Mutagens</topic><topic>Nanoparticles</topic><topic>Particle Size</topic><topic>Political aspects</topic><topic>Poly Adenosine Diphosphate Ribose - metabolism</topic><topic>Proteins</topic><topic>Scanning electron microscopy</topic><topic>Software</topic><topic>Solubility</topic><topic>Translocation, Genetic</topic><topic>Transmission electron microscopy</topic><topic>Variance analysis</topic><topic>Viscosity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Semisch, Annetta</creatorcontrib><creatorcontrib>Ohle, Julia</creatorcontrib><creatorcontrib>Witt, Barbara</creatorcontrib><creatorcontrib>Hartwig, Andrea</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Engineered Materials Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Civil Engineering Abstracts</collection><collection>ProQuest Engineering Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Engineering Database</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Particle and fibre toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Semisch, Annetta</au><au>Ohle, Julia</au><au>Witt, Barbara</au><au>Hartwig, Andrea</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxicity and genotoxicity of nano - and microparticulate copper oxide: role of solubility and intracellular bioavailability</atitle><jtitle>Particle and fibre toxicology</jtitle><addtitle>Part Fibre Toxicol</addtitle><date>2014-02-13</date><risdate>2014</risdate><volume>11</volume><issue>1</issue><spage>10</spage><epage>10</epage><pages>10-10</pages><artnum>10</artnum><issn>1743-8977</issn><eissn>1743-8977</eissn><abstract>Nano- or microscale copper oxide particles (CuO NP, CuO MP) are increasingly applied as catalysts or antimicrobial additives. This increases the risk of adverse health effects, since copper ions are cytotoxic under overload conditions.
The extra- and intracellular bioavailability of CuO NP and CuO MP were explored. In addition, different endpoints related to cytotoxicity as well as direct and indirect genotoxicity of the copper oxides and copper chloride (CuCl2) were compared.
Comprehensively characterized CuO NP and CuO MP were analysed regarding their copper ion release in model fluids. In all media investigated, CuO NP released far more copper ions than CuO MP, with most pronounced dissolution in artificial lysosomal fluid. CuO NP and CuCl2 caused a pronounced and dose dependent decrease of colony forming ability (CFA) in A549 and HeLa S3 cells, whereas CuO MP exerted no cytotoxicity at concentrations up to 50 μg/mL. Cell death induced by CuO NP was at least in part due to apoptosis, as determined by subdiploid DNA as well as via translocation of the apoptosis inducing factor (AIF) into the cell nucleus. Similarly, only CuO NP induced significant amounts of DNA strand breaks in HeLa S3 cells, whereas all three compounds elevated the level of H2O2-induced DNA strand breaks. Finally, all copper compounds diminished the H2O2-induced poly(ADP-ribosyl)ation, catalysed predominantly by poly(ADP-ribose)polymerase-1 (PARP-1); here, again, CuO NP exerted the strongest effect. Copper derived from CuO NP, CuO MP and CuCl2 accumulated in the soluble cytoplasmic and nuclear fractions of A549 cells, yielding similar concentrations in the cytoplasm but highest concentrations in the nucleus in case of CuO NP.
The results support the high cytotoxicity of CuO NP and CuCl2 and the missing cytotoxicity of CuO MP under the conditions applied. For these differences in cytotoxicity, extracellular copper ion levels due to dissolution of particles as well as differences in physicochemical properties of the particles like surface area may be of major relevance. Regarding direct and indirect genotoxicity, especially the high copper content in the cell nucleus derived after cell treatment with CuO NP appears to be decisive.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>24520990</pmid><doi>10.1186/1743-8977-11-10</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1743-8977 |
| ispartof | Particle and fibre toxicology, 2014-02, Vol.11 (1), p.10-10, Article 10 |
| issn | 1743-8977 1743-8977 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3943586 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; SpringerLink Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Springer Nature OA Free Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Apoptosis Apoptosis - drug effects Atoms & subatomic particles Bioavailability Biological Availability Caspase 3 - metabolism Caspase 7 - metabolism Cell death Cell Nucleus - metabolism Cell Survival - drug effects Copper - chemistry Copper - pharmacokinetics Copper - toxicity Cytotoxicity Deoxyribonucleic acid DNA DNA Damage Endotoxins - analysis Enzymes Fluids Health aspects HeLa Cells Humans Indicators and Reagents Life sciences Mass spectrometry Metal Nanoparticles - toxicity Micronucleus Tests Microscopy, Electron, Scanning Mutagens Nanoparticles Particle Size Political aspects Poly Adenosine Diphosphate Ribose - metabolism Proteins Scanning electron microscopy Software Solubility Translocation, Genetic Transmission electron microscopy Variance analysis Viscosity |
| title | Cytotoxicity and genotoxicity of nano - and microparticulate copper oxide: role of solubility and intracellular bioavailability |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T07%3A49%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cytotoxicity%20and%20genotoxicity%20of%20nano%20-%20and%20microparticulate%20copper%20oxide:%20role%20of%20solubility%20and%20intracellular%20bioavailability&rft.jtitle=Particle%20and%20fibre%20toxicology&rft.au=Semisch,%20Annetta&rft.date=2014-02-13&rft.volume=11&rft.issue=1&rft.spage=10&rft.epage=10&rft.pages=10-10&rft.artnum=10&rft.issn=1743-8977&rft.eissn=1743-8977&rft_id=info:doi/10.1186/1743-8977-11-10&rft_dat=%3Cgale_pubme%3EA539684067%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1504674804&rft_id=info:pmid/24520990&rft_galeid=A539684067&rfr_iscdi=true |