Involvement of reactive oxygen species in Microcystin-LR-induced cytogenotoxicity
Microcystin-LR (MCLR) is a potent hepatotoxin. Oxidative stress is thought to be implicated in the cytotoxicity of MCLR, but the mechanisms by which MCLR produces reactive oxygen species (ROS) are still unclear. This study investigated the role and possible sources of ROS generation in MCLR-induced...
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| Veröffentlicht in: | Free radical research 2007-12, Vol.41 (12), p.1326-1337 |
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| creator | Nong, Qingqing Komatsu, Masaharu Izumo, Kimiko Indo, Hiroko P. Xu, Baohui Aoyama, Kohji Majima, Hideyuki J. Horiuchi, Masahisa Morimoto, Kanehisa Takeuchi, Toru |
| description | Microcystin-LR (MCLR) is a potent hepatotoxin. Oxidative stress is thought to be implicated in the cytotoxicity of MCLR, but the mechanisms by which MCLR produces reactive oxygen species (ROS) are still unclear. This study investigated the role and possible sources of ROS generation in MCLR-induced cytogenotoxicity in HepG2, a human hepatoma cell line. MCLR increased DNA strand breaks, 8-hydroxydeoxiguanosine formation, lipid peroxidation, as well as LDH release, all of which were inhibited by ROS scavengers. ROS scavengers partly suppressed MCLR-induced cytotoxicity determined by the MTT assay. MCLR induced the generation of ROS, as confirmed by confocal microscopy with 2-[6-(4′-hydroxy)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid, and upregulated the expression of CYP2E1 mRNA. In addition, CYP2E1 inhibitors chlormethiazole and diallyl sulphide inhibited both ROS generation and cytotoxicity induced by MCLR. The results suggest that ROS contribute to MCLR-induced cytogenotoxicity. CYP2E1 might be a potential source responsible for ROS generation by MCLR. |
| doi_str_mv | 10.1080/10715760701704599 |
| format | Article |
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Oxidative stress is thought to be implicated in the cytotoxicity of MCLR, but the mechanisms by which MCLR produces reactive oxygen species (ROS) are still unclear. This study investigated the role and possible sources of ROS generation in MCLR-induced cytogenotoxicity in HepG2, a human hepatoma cell line. MCLR increased DNA strand breaks, 8-hydroxydeoxiguanosine formation, lipid peroxidation, as well as LDH release, all of which were inhibited by ROS scavengers. ROS scavengers partly suppressed MCLR-induced cytotoxicity determined by the MTT assay. MCLR induced the generation of ROS, as confirmed by confocal microscopy with 2-[6-(4′-hydroxy)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid, and upregulated the expression of CYP2E1 mRNA. In addition, CYP2E1 inhibitors chlormethiazole and diallyl sulphide inhibited both ROS generation and cytotoxicity induced by MCLR. The results suggest that ROS contribute to MCLR-induced cytogenotoxicity. CYP2E1 might be a potential source responsible for ROS generation by MCLR.</description><identifier>ISSN: 1071-5762</identifier><identifier>EISSN: 1029-2470</identifier><identifier>DOI: 10.1080/10715760701704599</identifier><identifier>PMID: 17963120</identifier><language>eng</language><publisher>England: Informa UK Ltd</publisher><subject>Bacterial Toxins - toxicity ; Carcinoma, Hepatocellular ; Cell Cycle - drug effects ; Cell Line, Tumor ; Comet Assay ; CYP2E1 ; Cytochrome P-450 Enzyme System - genetics ; cytogenotoxicity ; Deoxyguanosine - analogs & derivatives ; Deoxyguanosine - analysis ; Humans ; Immunohistochemistry ; L-Lactate Dehydrogenase - analysis ; Liver Neoplasms ; Microcystin-LR ; Microcystins - toxicity ; oxidative damage ; Polymerase Chain Reaction ; reactive oxygen species (ROS) ; Reactive Oxygen Species - metabolism ; RNA, Messenger - genetics</subject><ispartof>Free radical research, 2007-12, Vol.41 (12), p.1326-1337</ispartof><rights>2007 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-fae4160af0ad2346d55078568622da0ec3ae9b466bb7588ab5d08ff877fedf123</citedby><cites>FETCH-LOGICAL-c404t-fae4160af0ad2346d55078568622da0ec3ae9b466bb7588ab5d08ff877fedf123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1080/10715760701704599$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/10715760701704599$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,59620,60409,61194,61375</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17963120$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nong, Qingqing</creatorcontrib><creatorcontrib>Komatsu, Masaharu</creatorcontrib><creatorcontrib>Izumo, Kimiko</creatorcontrib><creatorcontrib>Indo, Hiroko P.</creatorcontrib><creatorcontrib>Xu, Baohui</creatorcontrib><creatorcontrib>Aoyama, Kohji</creatorcontrib><creatorcontrib>Majima, Hideyuki J.</creatorcontrib><creatorcontrib>Horiuchi, Masahisa</creatorcontrib><creatorcontrib>Morimoto, Kanehisa</creatorcontrib><creatorcontrib>Takeuchi, Toru</creatorcontrib><title>Involvement of reactive oxygen species in Microcystin-LR-induced cytogenotoxicity</title><title>Free radical research</title><addtitle>Free Radic Res</addtitle><description>Microcystin-LR (MCLR) is a potent hepatotoxin. Oxidative stress is thought to be implicated in the cytotoxicity of MCLR, but the mechanisms by which MCLR produces reactive oxygen species (ROS) are still unclear. This study investigated the role and possible sources of ROS generation in MCLR-induced cytogenotoxicity in HepG2, a human hepatoma cell line. MCLR increased DNA strand breaks, 8-hydroxydeoxiguanosine formation, lipid peroxidation, as well as LDH release, all of which were inhibited by ROS scavengers. ROS scavengers partly suppressed MCLR-induced cytotoxicity determined by the MTT assay. MCLR induced the generation of ROS, as confirmed by confocal microscopy with 2-[6-(4′-hydroxy)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid, and upregulated the expression of CYP2E1 mRNA. In addition, CYP2E1 inhibitors chlormethiazole and diallyl sulphide inhibited both ROS generation and cytotoxicity induced by MCLR. The results suggest that ROS contribute to MCLR-induced cytogenotoxicity. CYP2E1 might be a potential source responsible for ROS generation by MCLR.</description><subject>Bacterial Toxins - toxicity</subject><subject>Carcinoma, Hepatocellular</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Comet Assay</subject><subject>CYP2E1</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>cytogenotoxicity</subject><subject>Deoxyguanosine - analogs & derivatives</subject><subject>Deoxyguanosine - analysis</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>L-Lactate Dehydrogenase - analysis</subject><subject>Liver Neoplasms</subject><subject>Microcystin-LR</subject><subject>Microcystins - toxicity</subject><subject>oxidative damage</subject><subject>Polymerase Chain Reaction</subject><subject>reactive oxygen species (ROS)</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>RNA, Messenger - genetics</subject><issn>1071-5762</issn><issn>1029-2470</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1KAzEUhYMotlYfwI3MC4zezF9m0I0UfwoVUXQ9ZJIbmzJNSpLWzts7pQURoat7F993OBxCLilcUyjhhgKjOSuAAWWQ5VV1RIYUkipOMgbH25_RuAeSATnzfg5A0yxnp2RAWVWkNIEheZuYtW3XuEATIqsih1wEvcbIbrovNJFfotDoI22iFy2cFZ0P2sTT91gbuRIoI9EF25M22I0WOnTn5ETx1uPF_o7I5-PDx_g5nr4-Tcb301hkkIVYccxoAVwBl0maFTLPgZV5URZJIjmgSDlWTVYUTcPysuRNLqFUqmRMoVQ0SUeE7nL7Vt47VPXS6QV3XU2h3s5T_5und652znLVLFD-Gvs9euBuB2ijrFvwb-taWQfetdYpx43Qvk4P5d_-0WfI2zAT3GE9tytn-j0OtPsBl5SGyg</recordid><startdate>20071201</startdate><enddate>20071201</enddate><creator>Nong, Qingqing</creator><creator>Komatsu, Masaharu</creator><creator>Izumo, Kimiko</creator><creator>Indo, Hiroko P.</creator><creator>Xu, Baohui</creator><creator>Aoyama, Kohji</creator><creator>Majima, Hideyuki J.</creator><creator>Horiuchi, Masahisa</creator><creator>Morimoto, Kanehisa</creator><creator>Takeuchi, Toru</creator><general>Informa UK Ltd</general><general>Taylor & Francis</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></search><sort><creationdate>20071201</creationdate><title>Involvement of reactive oxygen species in Microcystin-LR-induced cytogenotoxicity</title><author>Nong, Qingqing ; Komatsu, Masaharu ; Izumo, Kimiko ; Indo, Hiroko P. ; Xu, Baohui ; Aoyama, Kohji ; Majima, Hideyuki J. ; Horiuchi, Masahisa ; Morimoto, Kanehisa ; Takeuchi, Toru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-fae4160af0ad2346d55078568622da0ec3ae9b466bb7588ab5d08ff877fedf123</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Bacterial Toxins - toxicity</topic><topic>Carcinoma, Hepatocellular</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Comet Assay</topic><topic>CYP2E1</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>cytogenotoxicity</topic><topic>Deoxyguanosine - analogs & derivatives</topic><topic>Deoxyguanosine - analysis</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>L-Lactate Dehydrogenase - analysis</topic><topic>Liver Neoplasms</topic><topic>Microcystin-LR</topic><topic>Microcystins - toxicity</topic><topic>oxidative damage</topic><topic>Polymerase Chain Reaction</topic><topic>reactive oxygen species (ROS)</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>RNA, Messenger - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nong, Qingqing</creatorcontrib><creatorcontrib>Komatsu, Masaharu</creatorcontrib><creatorcontrib>Izumo, Kimiko</creatorcontrib><creatorcontrib>Indo, Hiroko P.</creatorcontrib><creatorcontrib>Xu, Baohui</creatorcontrib><creatorcontrib>Aoyama, Kohji</creatorcontrib><creatorcontrib>Majima, Hideyuki J.</creatorcontrib><creatorcontrib>Horiuchi, Masahisa</creatorcontrib><creatorcontrib>Morimoto, Kanehisa</creatorcontrib><creatorcontrib>Takeuchi, Toru</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Free radical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nong, Qingqing</au><au>Komatsu, Masaharu</au><au>Izumo, Kimiko</au><au>Indo, Hiroko P.</au><au>Xu, Baohui</au><au>Aoyama, Kohji</au><au>Majima, Hideyuki J.</au><au>Horiuchi, Masahisa</au><au>Morimoto, Kanehisa</au><au>Takeuchi, Toru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Involvement of reactive oxygen species in Microcystin-LR-induced cytogenotoxicity</atitle><jtitle>Free radical research</jtitle><addtitle>Free Radic Res</addtitle><date>2007-12-01</date><risdate>2007</risdate><volume>41</volume><issue>12</issue><spage>1326</spage><epage>1337</epage><pages>1326-1337</pages><issn>1071-5762</issn><eissn>1029-2470</eissn><abstract>Microcystin-LR (MCLR) is a potent hepatotoxin. Oxidative stress is thought to be implicated in the cytotoxicity of MCLR, but the mechanisms by which MCLR produces reactive oxygen species (ROS) are still unclear. This study investigated the role and possible sources of ROS generation in MCLR-induced cytogenotoxicity in HepG2, a human hepatoma cell line. MCLR increased DNA strand breaks, 8-hydroxydeoxiguanosine formation, lipid peroxidation, as well as LDH release, all of which were inhibited by ROS scavengers. ROS scavengers partly suppressed MCLR-induced cytotoxicity determined by the MTT assay. MCLR induced the generation of ROS, as confirmed by confocal microscopy with 2-[6-(4′-hydroxy)phenoxy-3H-xanthen-3-on-9-yl]benzoic acid, and upregulated the expression of CYP2E1 mRNA. In addition, CYP2E1 inhibitors chlormethiazole and diallyl sulphide inhibited both ROS generation and cytotoxicity induced by MCLR. The results suggest that ROS contribute to MCLR-induced cytogenotoxicity. CYP2E1 might be a potential source responsible for ROS generation by MCLR.</abstract><cop>England</cop><pub>Informa UK Ltd</pub><pmid>17963120</pmid><doi>10.1080/10715760701704599</doi><tpages>12</tpages></addata></record> |
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| subjects | Bacterial Toxins - toxicity Carcinoma, Hepatocellular Cell Cycle - drug effects Cell Line, Tumor Comet Assay CYP2E1 Cytochrome P-450 Enzyme System - genetics cytogenotoxicity Deoxyguanosine - analogs & derivatives Deoxyguanosine - analysis Humans Immunohistochemistry L-Lactate Dehydrogenase - analysis Liver Neoplasms Microcystin-LR Microcystins - toxicity oxidative damage Polymerase Chain Reaction reactive oxygen species (ROS) Reactive Oxygen Species - metabolism RNA, Messenger - genetics |
| title | Involvement of reactive oxygen species in Microcystin-LR-induced cytogenotoxicity |
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