Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes
Titanium dioxide nanoparticles (nano-TiO₂) are widely used as a photocatalyst in air and water remediation. These nanoparticles are known to induce toxicity; however, their cytotoxic mechanism is not fully understood. In this study, we investigated the underlying mechanism of nano-TiO₂-induced cytot...
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| Veröffentlicht in: | Environmental and molecular mutagenesis 2008-06, Vol.49 (5), p.399-405 |
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| creator | Kang, Su Jin Kim, Byeong Mo Lee, Young Joon Chung, Hai Won |
| description | Titanium dioxide nanoparticles (nano-TiO₂) are widely used as a photocatalyst in air and water remediation. These nanoparticles are known to induce toxicity; however, their cytotoxic mechanism is not fully understood. In this study, we investigated the underlying mechanism of nano-TiO₂-induced cytotoxicity in peripheral blood lymphocytes. We examined the genotoxic effects of nano-TiO₂ in lymphocytes using alkaline single-cell gel electrophoresis (Comet) and cytokinesis-block micronucleus (CBMN) assays. Lymphocytes treated with nano-TiO₂ showed significantly increased micronucleus formation and DNA breakage. Western-blot analysis to identify proteins involved in the p53-mediated response to DNA damage revealed the accumulation of p53 and activation of DNA damage checkpoint kinases in nano-TiO₂-treated lymphocytes. However, p21 and bax, downstream targets of p53, were not affected, indicating that nano-TiO₂ does not stimulate transactivational activity of p53. The generation of reactive oxygen species (ROS) in nano-TiO₂-treated cells was also observed, andN-acetylcysteine (NAC) supplementation inhibited the level of nano-TiO₂-induced DNA damage. Given that ROS-induced DNA damage leads to p53 activation in the DNA damage response, our results suggest that nano-TiO₂ induces ROS generation in lymphocytes, thereby activating p53-mediated DNA damage checkpoint signals. Environ. Mol. Mutagen., 2008. |
| doi_str_mv | 10.1002/em.20399 |
| format | Article |
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These nanoparticles are known to induce toxicity; however, their cytotoxic mechanism is not fully understood. In this study, we investigated the underlying mechanism of nano-TiO₂-induced cytotoxicity in peripheral blood lymphocytes. We examined the genotoxic effects of nano-TiO₂ in lymphocytes using alkaline single-cell gel electrophoresis (Comet) and cytokinesis-block micronucleus (CBMN) assays. Lymphocytes treated with nano-TiO₂ showed significantly increased micronucleus formation and DNA breakage. Western-blot analysis to identify proteins involved in the p53-mediated response to DNA damage revealed the accumulation of p53 and activation of DNA damage checkpoint kinases in nano-TiO₂-treated lymphocytes. However, p21 and bax, downstream targets of p53, were not affected, indicating that nano-TiO₂ does not stimulate transactivational activity of p53. The generation of reactive oxygen species (ROS) in nano-TiO₂-treated cells was also observed, andN-acetylcysteine (NAC) supplementation inhibited the level of nano-TiO₂-induced DNA damage. Given that ROS-induced DNA damage leads to p53 activation in the DNA damage response, our results suggest that nano-TiO₂ induces ROS generation in lymphocytes, thereby activating p53-mediated DNA damage checkpoint signals. Environ. Mol. Mutagen., 2008.</description><identifier>ISSN: 0893-6692</identifier><identifier>EISSN: 1098-2280</identifier><identifier>DOI: 10.1002/em.20399</identifier><identifier>PMID: 18418868</identifier><identifier>CODEN: EMMUEG</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adult ; Biological and medical sciences ; Blotting, Western ; Cell physiology ; Cell Survival - drug effects ; Cell transformation and carcinogenesis. 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Biological and molecular evolution ; Humans ; Lymphocytes - cytology ; Lymphocytes - drug effects ; Lymphocytes - metabolism ; Medical sciences ; micronuclei ; Micronuclei, Chromosome-Defective - chemically induced ; Micronucleus Tests ; Molecular and cellular biology ; Mutagens - toxicity ; Nanoparticles ; p53 damage response ; Particle Size ; Reactive Oxygen Species - metabolism ; ROS ; single-cell gel electrophoresis ; Titanium - toxicity ; titanium dioxide nanoparticles ; Toxicology ; Tumor Suppressor Protein p53 - metabolism</subject><ispartof>Environmental and molecular mutagenesis, 2008-06, Vol.49 (5), p.399-405</ispartof><rights>Copyright © 2008 Wiley‐Liss, Inc.</rights><rights>2008 INIST-CNRS</rights><rights>(c) 2008 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4779-61d547b23f375848c45fd51309fd1c52ca7bf701520df1dbef56052bac0becd23</citedby><cites>FETCH-LOGICAL-c4779-61d547b23f375848c45fd51309fd1c52ca7bf701520df1dbef56052bac0becd23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fem.20399$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fem.20399$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20452517$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18418868$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kang, Su Jin</creatorcontrib><creatorcontrib>Kim, Byeong Mo</creatorcontrib><creatorcontrib>Lee, Young Joon</creatorcontrib><creatorcontrib>Chung, Hai Won</creatorcontrib><title>Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes</title><title>Environmental and molecular mutagenesis</title><addtitle>Environ. Mol. Mutagen</addtitle><description>Titanium dioxide nanoparticles (nano-TiO₂) are widely used as a photocatalyst in air and water remediation. These nanoparticles are known to induce toxicity; however, their cytotoxic mechanism is not fully understood. In this study, we investigated the underlying mechanism of nano-TiO₂-induced cytotoxicity in peripheral blood lymphocytes. We examined the genotoxic effects of nano-TiO₂ in lymphocytes using alkaline single-cell gel electrophoresis (Comet) and cytokinesis-block micronucleus (CBMN) assays. Lymphocytes treated with nano-TiO₂ showed significantly increased micronucleus formation and DNA breakage. Western-blot analysis to identify proteins involved in the p53-mediated response to DNA damage revealed the accumulation of p53 and activation of DNA damage checkpoint kinases in nano-TiO₂-treated lymphocytes. However, p21 and bax, downstream targets of p53, were not affected, indicating that nano-TiO₂ does not stimulate transactivational activity of p53. The generation of reactive oxygen species (ROS) in nano-TiO₂-treated cells was also observed, andN-acetylcysteine (NAC) supplementation inhibited the level of nano-TiO₂-induced DNA damage. Given that ROS-induced DNA damage leads to p53 activation in the DNA damage response, our results suggest that nano-TiO₂ induces ROS generation in lymphocytes, thereby activating p53-mediated DNA damage checkpoint signals. Environ. Mol. Mutagen., 2008.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cell physiology</subject><subject>Cell Survival - drug effects</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Cells, Cultured</subject><subject>Comet Assay</subject><subject>DNA Damage</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Humans</subject><subject>Lymphocytes - cytology</subject><subject>Lymphocytes - drug effects</subject><subject>Lymphocytes - metabolism</subject><subject>Medical sciences</subject><subject>micronuclei</subject><subject>Micronuclei, Chromosome-Defective - chemically induced</subject><subject>Micronucleus Tests</subject><subject>Molecular and cellular biology</subject><subject>Mutagens - toxicity</subject><subject>Nanoparticles</subject><subject>p53 damage response</subject><subject>Particle Size</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>ROS</subject><subject>single-cell gel electrophoresis</subject><subject>Titanium - toxicity</subject><subject>titanium dioxide nanoparticles</subject><subject>Toxicology</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>0893-6692</issn><issn>1098-2280</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10MtuFDEQBVArApEhIPEF4A0Sm07K7nbbXkIeA1IeQkkUiY3ltssTJ_2S3VEyf0-HGcKKVW2O6lZdQj4w2GcA_AC7fQ6l1jtkwUCrgnMFr8gClC6LutZ8l7zN-Q6AsUrzN2SXqYopVasFcVdxsn186KiPw1P0SHvbD6NNU3QtZjqluFphoqMoiw59tBN66m1nV0gT5nHoM9LY0xFTHG8x2ZY27TB42q678XZw6wnzO_I62Dbj--3cI9cnx1eH34vTi-WPw6-nhauk1EXNvKhkw8tQSqEq5SoRvGAl6OCZE9xZ2QQJTHDwgfkGg6hB8MY6aNB5Xu6RL5u9Lg05JwxmTLGzaW0YmOeeDHbmT08z_bih40Mzv_UPbouZwectsNnZNiTbu5hfHIdKcMHk7IqNe4wtrv8baI7P_gZvfcwTPr14m-5NLee_zc350ugl_DxiJ7_Mt9l_2vhgB2NXab7h-pLD3ApoUJJB-RtzjZeM</recordid><startdate>200806</startdate><enddate>200806</enddate><creator>Kang, Su Jin</creator><creator>Kim, Byeong Mo</creator><creator>Lee, Young Joon</creator><creator>Chung, Hai Won</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>FBQ</scope><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>200806</creationdate><title>Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes</title><author>Kang, Su Jin ; Kim, Byeong Mo ; Lee, Young Joon ; Chung, Hai Won</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4779-61d547b23f375848c45fd51309fd1c52ca7bf701520df1dbef56052bac0becd23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cell physiology</topic><topic>Cell Survival - drug effects</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Cells, Cultured</topic><topic>Comet Assay</topic><topic>DNA Damage</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Humans</topic><topic>Lymphocytes - cytology</topic><topic>Lymphocytes - drug effects</topic><topic>Lymphocytes - metabolism</topic><topic>Medical sciences</topic><topic>micronuclei</topic><topic>Micronuclei, Chromosome-Defective - chemically induced</topic><topic>Micronucleus Tests</topic><topic>Molecular and cellular biology</topic><topic>Mutagens - toxicity</topic><topic>Nanoparticles</topic><topic>p53 damage response</topic><topic>Particle Size</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>ROS</topic><topic>single-cell gel electrophoresis</topic><topic>Titanium - toxicity</topic><topic>titanium dioxide nanoparticles</topic><topic>Toxicology</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Su Jin</creatorcontrib><creatorcontrib>Kim, Byeong Mo</creatorcontrib><creatorcontrib>Lee, Young Joon</creatorcontrib><creatorcontrib>Chung, Hai Won</creatorcontrib><collection>AGRIS</collection><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Environmental and molecular mutagenesis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Su Jin</au><au>Kim, Byeong Mo</au><au>Lee, Young Joon</au><au>Chung, Hai Won</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes</atitle><jtitle>Environmental and molecular mutagenesis</jtitle><addtitle>Environ. 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Western-blot analysis to identify proteins involved in the p53-mediated response to DNA damage revealed the accumulation of p53 and activation of DNA damage checkpoint kinases in nano-TiO₂-treated lymphocytes. However, p21 and bax, downstream targets of p53, were not affected, indicating that nano-TiO₂ does not stimulate transactivational activity of p53. The generation of reactive oxygen species (ROS) in nano-TiO₂-treated cells was also observed, andN-acetylcysteine (NAC) supplementation inhibited the level of nano-TiO₂-induced DNA damage. Given that ROS-induced DNA damage leads to p53 activation in the DNA damage response, our results suggest that nano-TiO₂ induces ROS generation in lymphocytes, thereby activating p53-mediated DNA damage checkpoint signals. Environ. Mol. Mutagen., 2008.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>18418868</pmid><doi>10.1002/em.20399</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Biological and medical sciences Blotting, Western Cell physiology Cell Survival - drug effects Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cells, Cultured Comet Assay DNA Damage Female Fundamental and applied biological sciences. Psychology Genetics of eukaryotes. Biological and molecular evolution Humans Lymphocytes - cytology Lymphocytes - drug effects Lymphocytes - metabolism Medical sciences micronuclei Micronuclei, Chromosome-Defective - chemically induced Micronucleus Tests Molecular and cellular biology Mutagens - toxicity Nanoparticles p53 damage response Particle Size Reactive Oxygen Species - metabolism ROS single-cell gel electrophoresis Titanium - toxicity titanium dioxide nanoparticles Toxicology Tumor Suppressor Protein p53 - metabolism |
| title | Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes |
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