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Cytotoxicity, DNA damage, and apoptosis induced by titanium dioxide nanoparticles in human non-small cell lung cancer A549 cells
Concerns about the risk of titanium dioxide nanoparticles (TiO₂NPs) to human health and environment are gradually increasing due to their wide range of applications. In this study, cytotoxicity, DNA damage, and apoptosis induced by TiO₂NPs (5 nm) in A549 cells were investigated. The 3-(4,5-dimethylt...
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| Published in: | Environmental science and pollution research international 2015-04, Vol.22 (7), p.5519-5530 |
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| creator | Wang, Yurong Cui, Haiyan Zhou, Jiaping Li, Fengjuan Wang, Jinju Chen, Mianhua Liu, Qingdai |
| description | Concerns about the risk of titanium dioxide nanoparticles (TiO₂NPs) to human health and environment are gradually increasing due to their wide range of applications. In this study, cytotoxicity, DNA damage, and apoptosis induced by TiO₂NPs (5 nm) in A549 cells were investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays revealed the time- and concentration-dependent cytotoxic effects of TiO₂NPs in a concentration range of 50 to 200 μg/mL. A statistically significant (p |
| doi_str_mv | 10.1007/s11356-014-3717-7 |
| format | article |
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In this study, cytotoxicity, DNA damage, and apoptosis induced by TiO₂NPs (5 nm) in A549 cells were investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays revealed the time- and concentration-dependent cytotoxic effects of TiO₂NPs in a concentration range of 50 to 200 μg/mL. A statistically significant (p < 0.05) induction in DNA damage was observed by the comet assay in cells exposed to 50 to 200 μg/mL TiO₂NPs for 48 h. A significant (p < 0.05) induction in micronucleus formation determined by 4,6-diamino-2-phenylindole (DAPI) staining was also observed at the above concentrations. Typical apoptotic morphological feature and apoptotic bodies in A549 cells induced by TiO₂NPs at the above concentrations were observed by scanning electron micrographs. Flow cytometric analysis demonstrated that the cells treated with TiO₂NPs at concentrations of 100 and 200 μg/mL showed a significant G₂/M phase arrest and a significant increased proportion of apoptotic cells. TiO₂NPs also disrupted the mitochondrial membrane potential evaluated by rhodamine 123 staining. Further analysis by quantitative real-time PCR (qRT-PCR) indicated that the expression of caspase-3 and caspase-9 messenger RNA (mRNA) was increased significantly at the concentrations of 100 and 200 μg/mL TiO₂NPs for 48 h. Taken together, these findings suggest that TiO₂NPs can inhibit A549 cell proliferation, cause DNA damage, and induce apoptosis via a mechanism primarily involving the activation of the intrinsic mitochondrial pathway. The assay data provide strong evidence that TiO₂NPs can induce cytotoxicity, significant DNA damage, and apoptosis of A549 cells, suggesting that exposure to TiO₂NPs could cause cell injury and be hazardous to health.</description><identifier>ISSN: 0944-1344</identifier><identifier>EISSN: 1614-7499</identifier><identifier>DOI: 10.1007/s11356-014-3717-7</identifier><identifier>PMID: 25339530</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Air pollution ; Analysis of Variance ; Apoptosis ; Apoptosis - drug effects ; Aquatic Pollution ; Assaying ; Atmospheric Protection/Air Quality Control/Air Pollution ; Bioassays ; Carcinogens, Environmental - toxicity ; caspase-3 ; caspase-9 ; Cell culture ; Cell Line, Tumor ; cell proliferation ; Comet Assay ; Cytotoxicity ; Damage ; Deoxyribonucleic acid ; DNA ; DNA Damage ; Dose-Response Relationship, Drug ; Earth and Environmental Science ; Ecotoxicology ; Environment ; Environmental changes ; Environmental Chemistry ; Environmental Health ; Environmental science ; Flow Cytometry ; G2 Phase Cell Cycle Checkpoints - drug effects ; Health ; Human ; human health ; Humans ; Indoles ; Laboratories ; Lung cancer ; lung neoplasms ; membrane potential ; messenger RNA ; Metal Nanoparticles - toxicity ; Micronucleus Tests ; mitochondrial membrane ; Nanoparticles ; quantitative analysis ; quantitative polymerase chain reaction ; Real-Time Polymerase Chain Reaction ; Research Article ; reverse transcriptase polymerase chain reaction ; risk ; Staining ; Studies ; Tetrazolium Salts ; Thiazoles ; Titanium ; Titanium - toxicity ; Titanium dioxide ; Titanium oxide powders ; Toxicity ; Waste Water Technology ; Water Management ; Water Pollution Control</subject><ispartof>Environmental science and pollution research international, 2015-04, Vol.22 (7), p.5519-5530</ispartof><rights>Springer-Verlag Berlin Heidelberg 2014</rights><rights>Springer-Verlag Berlin Heidelberg 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-15871252672c56e9e6371acb82ba71ef4b558fcdf371f1c1c6d0533408d8b15b3</citedby><cites>FETCH-LOGICAL-c532t-15871252672c56e9e6371acb82ba71ef4b558fcdf371f1c1c6d0533408d8b15b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1664737019/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$H</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1664737019?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,776,780,11667,27901,27902,36037,36038,44339,74638</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25339530$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yurong</creatorcontrib><creatorcontrib>Cui, Haiyan</creatorcontrib><creatorcontrib>Zhou, Jiaping</creatorcontrib><creatorcontrib>Li, Fengjuan</creatorcontrib><creatorcontrib>Wang, Jinju</creatorcontrib><creatorcontrib>Chen, Mianhua</creatorcontrib><creatorcontrib>Liu, Qingdai</creatorcontrib><title>Cytotoxicity, DNA damage, and apoptosis induced by titanium dioxide nanoparticles in human non-small cell lung cancer A549 cells</title><title>Environmental science and pollution research international</title><addtitle>Environ Sci Pollut Res</addtitle><addtitle>Environ Sci Pollut Res Int</addtitle><description>Concerns about the risk of titanium dioxide nanoparticles (TiO₂NPs) to human health and environment are gradually increasing due to their wide range of applications. In this study, cytotoxicity, DNA damage, and apoptosis induced by TiO₂NPs (5 nm) in A549 cells were investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays revealed the time- and concentration-dependent cytotoxic effects of TiO₂NPs in a concentration range of 50 to 200 μg/mL. A statistically significant (p < 0.05) induction in DNA damage was observed by the comet assay in cells exposed to 50 to 200 μg/mL TiO₂NPs for 48 h. A significant (p < 0.05) induction in micronucleus formation determined by 4,6-diamino-2-phenylindole (DAPI) staining was also observed at the above concentrations. Typical apoptotic morphological feature and apoptotic bodies in A549 cells induced by TiO₂NPs at the above concentrations were observed by scanning electron micrographs. Flow cytometric analysis demonstrated that the cells treated with TiO₂NPs at concentrations of 100 and 200 μg/mL showed a significant G₂/M phase arrest and a significant increased proportion of apoptotic cells. TiO₂NPs also disrupted the mitochondrial membrane potential evaluated by rhodamine 123 staining. Further analysis by quantitative real-time PCR (qRT-PCR) indicated that the expression of caspase-3 and caspase-9 messenger RNA (mRNA) was increased significantly at the concentrations of 100 and 200 μg/mL TiO₂NPs for 48 h. Taken together, these findings suggest that TiO₂NPs can inhibit A549 cell proliferation, cause DNA damage, and induce apoptosis via a mechanism primarily involving the activation of the intrinsic mitochondrial pathway. The assay data provide strong evidence that TiO₂NPs can induce cytotoxicity, significant DNA damage, and apoptosis of A549 cells, suggesting that exposure to TiO₂NPs could cause cell injury and be hazardous to health.</description><subject>Air pollution</subject><subject>Analysis of Variance</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Aquatic Pollution</subject><subject>Assaying</subject><subject>Atmospheric Protection/Air Quality Control/Air Pollution</subject><subject>Bioassays</subject><subject>Carcinogens, Environmental - toxicity</subject><subject>caspase-3</subject><subject>caspase-9</subject><subject>Cell culture</subject><subject>Cell Line, Tumor</subject><subject>cell proliferation</subject><subject>Comet Assay</subject><subject>Cytotoxicity</subject><subject>Damage</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Earth and Environmental Science</subject><subject>Ecotoxicology</subject><subject>Environment</subject><subject>Environmental changes</subject><subject>Environmental Chemistry</subject><subject>Environmental Health</subject><subject>Environmental science</subject><subject>Flow Cytometry</subject><subject>G2 Phase Cell Cycle Checkpoints - drug effects</subject><subject>Health</subject><subject>Human</subject><subject>human health</subject><subject>Humans</subject><subject>Indoles</subject><subject>Laboratories</subject><subject>Lung cancer</subject><subject>lung neoplasms</subject><subject>membrane potential</subject><subject>messenger RNA</subject><subject>Metal Nanoparticles - toxicity</subject><subject>Micronucleus Tests</subject><subject>mitochondrial membrane</subject><subject>Nanoparticles</subject><subject>quantitative analysis</subject><subject>quantitative polymerase chain reaction</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Research Article</subject><subject>reverse transcriptase polymerase chain reaction</subject><subject>risk</subject><subject>Staining</subject><subject>Studies</subject><subject>Tetrazolium Salts</subject><subject>Thiazoles</subject><subject>Titanium</subject><subject>Titanium - toxicity</subject><subject>Titanium dioxide</subject><subject>Titanium oxide powders</subject><subject>Toxicity</subject><subject>Waste Water Technology</subject><subject>Water Management</subject><subject>Water Pollution 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DNA damage, and apoptosis induced by titanium dioxide nanoparticles in human non-small cell lung cancer A549 cells</title><author>Wang, Yurong ; Cui, Haiyan ; Zhou, Jiaping ; Li, Fengjuan ; Wang, Jinju ; Chen, Mianhua ; Liu, Qingdai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-15871252672c56e9e6371acb82ba71ef4b558fcdf371f1c1c6d0533408d8b15b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Air pollution</topic><topic>Analysis of Variance</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Aquatic Pollution</topic><topic>Assaying</topic><topic>Atmospheric Protection/Air Quality Control/Air Pollution</topic><topic>Bioassays</topic><topic>Carcinogens, Environmental - toxicity</topic><topic>caspase-3</topic><topic>caspase-9</topic><topic>Cell culture</topic><topic>Cell Line, Tumor</topic><topic>cell proliferation</topic><topic>Comet 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Int</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>22</volume><issue>7</issue><spage>5519</spage><epage>5530</epage><pages>5519-5530</pages><issn>0944-1344</issn><eissn>1614-7499</eissn><abstract>Concerns about the risk of titanium dioxide nanoparticles (TiO₂NPs) to human health and environment are gradually increasing due to their wide range of applications. In this study, cytotoxicity, DNA damage, and apoptosis induced by TiO₂NPs (5 nm) in A549 cells were investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays revealed the time- and concentration-dependent cytotoxic effects of TiO₂NPs in a concentration range of 50 to 200 μg/mL. A statistically significant (p < 0.05) induction in DNA damage was observed by the comet assay in cells exposed to 50 to 200 μg/mL TiO₂NPs for 48 h. A significant (p < 0.05) induction in micronucleus formation determined by 4,6-diamino-2-phenylindole (DAPI) staining was also observed at the above concentrations. Typical apoptotic morphological feature and apoptotic bodies in A549 cells induced by TiO₂NPs at the above concentrations were observed by scanning electron micrographs. Flow cytometric analysis demonstrated that the cells treated with TiO₂NPs at concentrations of 100 and 200 μg/mL showed a significant G₂/M phase arrest and a significant increased proportion of apoptotic cells. TiO₂NPs also disrupted the mitochondrial membrane potential evaluated by rhodamine 123 staining. Further analysis by quantitative real-time PCR (qRT-PCR) indicated that the expression of caspase-3 and caspase-9 messenger RNA (mRNA) was increased significantly at the concentrations of 100 and 200 μg/mL TiO₂NPs for 48 h. Taken together, these findings suggest that TiO₂NPs can inhibit A549 cell proliferation, cause DNA damage, and induce apoptosis via a mechanism primarily involving the activation of the intrinsic mitochondrial pathway. The assay data provide strong evidence that TiO₂NPs can induce cytotoxicity, significant DNA damage, and apoptosis of A549 cells, suggesting that exposure to TiO₂NPs could cause cell injury and be hazardous to health.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>25339530</pmid><doi>10.1007/s11356-014-3717-7</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0944-1344 |
| ispartof | Environmental science and pollution research international, 2015-04, Vol.22 (7), p.5519-5530 |
| issn | 0944-1344 1614-7499 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1677907778 |
| source | ABI/INFORM Global; Springer Nature |
| subjects | Air pollution Analysis of Variance Apoptosis Apoptosis - drug effects Aquatic Pollution Assaying Atmospheric Protection/Air Quality Control/Air Pollution Bioassays Carcinogens, Environmental - toxicity caspase-3 caspase-9 Cell culture Cell Line, Tumor cell proliferation Comet Assay Cytotoxicity Damage Deoxyribonucleic acid DNA DNA Damage Dose-Response Relationship, Drug Earth and Environmental Science Ecotoxicology Environment Environmental changes Environmental Chemistry Environmental Health Environmental science Flow Cytometry G2 Phase Cell Cycle Checkpoints - drug effects Health Human human health Humans Indoles Laboratories Lung cancer lung neoplasms membrane potential messenger RNA Metal Nanoparticles - toxicity Micronucleus Tests mitochondrial membrane Nanoparticles quantitative analysis quantitative polymerase chain reaction Real-Time Polymerase Chain Reaction Research Article reverse transcriptase polymerase chain reaction risk Staining Studies Tetrazolium Salts Thiazoles Titanium Titanium - toxicity Titanium dioxide Titanium oxide powders Toxicity Waste Water Technology Water Management Water Pollution Control |
| title | Cytotoxicity, DNA damage, and apoptosis induced by titanium dioxide nanoparticles in human non-small cell lung cancer A549 cells |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T09%3A52%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cytotoxicity,%20DNA%20damage,%20and%20apoptosis%20induced%20by%20titanium%20dioxide%20nanoparticles%20in%20human%20non-small%20cell%20lung%20cancer%20A549%20cells&rft.jtitle=Environmental%20science%20and%20pollution%20research%20international&rft.au=Wang,%20Yurong&rft.date=2015-04-01&rft.volume=22&rft.issue=7&rft.spage=5519&rft.epage=5530&rft.pages=5519-5530&rft.issn=0944-1344&rft.eissn=1614-7499&rft_id=info:doi/10.1007/s11356-014-3717-7&rft_dat=%3Cproquest_cross%3E1673384881%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c532t-15871252672c56e9e6371acb82ba71ef4b558fcdf371f1c1c6d0533408d8b15b3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1664737019&rft_id=info:pmid/25339530&rfr_iscdi=true |