Effects of Brevetoxins on Murine Myeloma SP2/O Cells: Aberrant Cellular Division
Massive deaths of manatees (Trichechus manatus latirostris) during the red tide seasons have been attributed to brevetoxins produced by the dinoflagellate Karenia brevis (formerly Ptychodiscus breve and Gymnodinium breve). Although these toxins have been found in macrophages and lymphocytes in the l...
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description | Massive deaths of manatees (Trichechus manatus latirostris) during the red tide seasons have been attributed to brevetoxins produced by the dinoflagellate Karenia brevis (formerly Ptychodiscus breve and Gymnodinium breve). Although these toxins have been found in macrophages and lymphocytes in the lung, liver, and secondary lymphoid tissues of these animals, the molecular mechanisms of brevetoxicosis have not yet been identified. To investigate the effects of brevetoxins on immune cells, a murine myeloma cell line (SP2/O) was used as a model for in vitro studies. By adding brevetoxins to cultures of the SP2/O cells at concentrations ranging from 20 to 600 ng/ml, an apparent increase in proliferation was observed at around 2 hours post challenge as compared to the unchallenged cell cultures. This was followed by a drop in cell number at around 3 hours, suggesting an aberrant effect of brevetoxins on cellular division, the cells generated at 2 hours being apparently short-lived. In situ immunochemical staining of the SP2/O cells at 1 and 2 hour post challenge showed an accumulation of the toxins in the nucleus. A 21-k Da protein was subsequently isolated from the SP2/O cells as having brevetoxin-binding properties, and immunologically identified as p21, a nuclear factor known to down-regulate cellular proliferation through inhibition of cyclindependent kinases. These data are the first on a possible effect of brevetoxins on the cell cycle via binding to p21, a phenomenon that needs to be further investigated and validated in normal immune cells. |
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Although these toxins have been found in macrophages and lymphocytes in the lung, liver, and secondary lymphoid tissues of these animals, the molecular mechanisms of brevetoxicosis have not yet been identified. To investigate the effects of brevetoxins on immune cells, a murine myeloma cell line (SP2/O) was used as a model for in vitro studies. By adding brevetoxins to cultures of the SP2/O cells at concentrations ranging from 20 to 600 ng/ml, an apparent increase in proliferation was observed at around 2 hours post challenge as compared to the unchallenged cell cultures. This was followed by a drop in cell number at around 3 hours, suggesting an aberrant effect of brevetoxins on cellular division, the cells generated at 2 hours being apparently short-lived. In situ immunochemical staining of the SP2/O cells at 1 and 2 hour post challenge showed an accumulation of the toxins in the nucleus. A 21-k Da protein was subsequently isolated from the SP2/O cells as having brevetoxin-binding properties, and immunologically identified as p21, a nuclear factor known to down-regulate cellular proliferation through inhibition of cyclindependent kinases. These data are the first on a possible effect of brevetoxins on the cell cycle via binding to p21, a phenomenon that needs to be further investigated and validated in normal immune cells.</description><identifier>ISSN: 1091-5818</identifier><identifier>EISSN: 1092-874X</identifier><identifier>DOI: 10.1080/10915810305095</identifier><identifier>PMID: 12745987</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animal, plant and microbial ecology ; Animals ; Applied ecology ; Biological and medical sciences ; Blotting, Western ; Carrier Proteins - metabolism ; Cell Division - drug effects ; Cell Nucleus - drug effects ; Cell Nucleus - metabolism ; Cell Survival - drug effects ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins - metabolism ; Dinoflagellida ; Dose-Response Relationship, Drug ; Ecotoxicology, biological effects of pollution ; Fundamental and applied biological sciences. Psychology ; Gymnodinium ; Immunohistochemistry ; Karenia brevis ; Marine and brackish environment ; Marine Toxins - immunology ; Marine Toxins - metabolism ; Marine Toxins - toxicity ; Medical sciences ; Mice ; Oxocins - immunology ; Oxocins - metabolism ; Oxocins - toxicity ; Plant poisons toxicology ; Plasmacytoma - pathology ; Ptychodiscus breve ; Toxicology ; Trichechus ; Trichechus manatus latirostris ; Tumor Cells, Cultured - drug effects ; Tumor Cells, Cultured - metabolism ; Tumor Cells, Cultured - pathology</subject><ispartof>International journal of toxicology, 2003-03, Vol.22 (2), p.73-80</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-1b5c428e262a530e515f3773b465875fb6938666aee268f10c1ef825fd3f9923</citedby><cites>FETCH-LOGICAL-c388t-1b5c428e262a530e515f3773b465875fb6938666aee268f10c1ef825fd3f9923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1080/10915810305095$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1080/10915810305095$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21819,27924,27925,43621,43622</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14763178$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12745987$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, Thomas K.</creatorcontrib><creatorcontrib>Derby, Melissa</creatorcontrib><creatorcontrib>Martin, Dean F.</creatorcontrib><creatorcontrib>Wright, Scott D.</creatorcontrib><creatorcontrib>Dao, My Lien</creatorcontrib><title>Effects of Brevetoxins on Murine Myeloma SP2/O Cells: Aberrant Cellular Division</title><title>International journal of toxicology</title><addtitle>Int J Toxicol</addtitle><description>Massive deaths of manatees (Trichechus manatus latirostris) during the red tide seasons have been attributed to brevetoxins produced by the dinoflagellate Karenia brevis (formerly Ptychodiscus breve and Gymnodinium breve). Although these toxins have been found in macrophages and lymphocytes in the lung, liver, and secondary lymphoid tissues of these animals, the molecular mechanisms of brevetoxicosis have not yet been identified. To investigate the effects of brevetoxins on immune cells, a murine myeloma cell line (SP2/O) was used as a model for in vitro studies. By adding brevetoxins to cultures of the SP2/O cells at concentrations ranging from 20 to 600 ng/ml, an apparent increase in proliferation was observed at around 2 hours post challenge as compared to the unchallenged cell cultures. This was followed by a drop in cell number at around 3 hours, suggesting an aberrant effect of brevetoxins on cellular division, the cells generated at 2 hours being apparently short-lived. In situ immunochemical staining of the SP2/O cells at 1 and 2 hour post challenge showed an accumulation of the toxins in the nucleus. A 21-k Da protein was subsequently isolated from the SP2/O cells as having brevetoxin-binding properties, and immunologically identified as p21, a nuclear factor known to down-regulate cellular proliferation through inhibition of cyclindependent kinases. These data are the first on a possible effect of brevetoxins on the cell cycle via binding to p21, a phenomenon that needs to be further investigated and validated in normal immune cells.</description><subject>Animal, plant and microbial ecology</subject><subject>Animals</subject><subject>Applied ecology</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Division - drug effects</subject><subject>Cell Nucleus - drug effects</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Survival - drug effects</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclins - metabolism</subject><subject>Dinoflagellida</subject><subject>Dose-Response Relationship, Drug</subject><subject>Ecotoxicology, biological effects of pollution</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gymnodinium</subject><subject>Immunohistochemistry</subject><subject>Karenia brevis</subject><subject>Marine and brackish environment</subject><subject>Marine Toxins - immunology</subject><subject>Marine Toxins - metabolism</subject><subject>Marine Toxins - toxicity</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Oxocins - immunology</subject><subject>Oxocins - metabolism</subject><subject>Oxocins - toxicity</subject><subject>Plant poisons toxicology</subject><subject>Plasmacytoma - pathology</subject><subject>Ptychodiscus breve</subject><subject>Toxicology</subject><subject>Trichechus</subject><subject>Trichechus manatus latirostris</subject><subject>Tumor Cells, Cultured - drug effects</subject><subject>Tumor Cells, Cultured - metabolism</subject><subject>Tumor Cells, Cultured - pathology</subject><issn>1091-5818</issn><issn>1092-874X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM9PwjAUxxujEUSvHs0uejGD_ljXzhsi_kggkMjB29KVVzMyNmw3Iv-9FZYQD576Xt-n39d8ELomuE-wxAOCE8IlwQxznPAT1PUXNJQi-jjd1yT0U9lBF86tMMax4OQcdQgVEU-k6KL52BjQtQsqEzxa2EJdfeelb8tg2ti8hGC6g6Jaq-B9TgezYARF4R6CYQbWqrLe902hbPCUb3OXV-UlOjOqcHDVnj20eB4vRq_hZPbyNhpOQs2krEOScR1RCTSmijMMnHDDhGBZFHMpuMnihMk4jhV4RBqCNQEjKTdLZpKEsh66O8RubPXVgKvTde60_4wqoWpcSgQVSSQjD_YPoLaVcxZMurH5WtldSnD6qzD9q9A_uGmTm2wNyyPeOvPAbQsop1VhvAeduyMXiZgRIT13f-Cc-oR0VTW29EL-W_sD5bGC2g</recordid><startdate>20030301</startdate><enddate>20030301</enddate><creator>Han, Thomas K.</creator><creator>Derby, Melissa</creator><creator>Martin, Dean F.</creator><creator>Wright, Scott D.</creator><creator>Dao, My Lien</creator><general>SAGE Publications</general><general>Taylor & Francis</general><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><scope>7U7</scope><scope>C1K</scope><scope>F1W</scope><scope>H95</scope><scope>L.G</scope><scope>M7N</scope></search><sort><creationdate>20030301</creationdate><title>Effects of Brevetoxins on Murine Myeloma SP2/O Cells: Aberrant Cellular Division</title><author>Han, Thomas K. ; Derby, Melissa ; Martin, Dean F. ; Wright, Scott D. ; Dao, My Lien</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c388t-1b5c428e262a530e515f3773b465875fb6938666aee268f10c1ef825fd3f9923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animal, plant and microbial ecology</topic><topic>Animals</topic><topic>Applied ecology</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell Division - drug effects</topic><topic>Cell Nucleus - drug effects</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Survival - drug effects</topic><topic>Cyclin-Dependent Kinase Inhibitor p21</topic><topic>Cyclins - metabolism</topic><topic>Dinoflagellida</topic><topic>Dose-Response Relationship, Drug</topic><topic>Ecotoxicology, biological effects of pollution</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gymnodinium</topic><topic>Immunohistochemistry</topic><topic>Karenia brevis</topic><topic>Marine and brackish environment</topic><topic>Marine Toxins - immunology</topic><topic>Marine Toxins - metabolism</topic><topic>Marine Toxins - toxicity</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Oxocins - immunology</topic><topic>Oxocins - metabolism</topic><topic>Oxocins - toxicity</topic><topic>Plant poisons toxicology</topic><topic>Plasmacytoma - pathology</topic><topic>Ptychodiscus breve</topic><topic>Toxicology</topic><topic>Trichechus</topic><topic>Trichechus manatus latirostris</topic><topic>Tumor Cells, Cultured - drug effects</topic><topic>Tumor Cells, Cultured - metabolism</topic><topic>Tumor Cells, Cultured - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, Thomas K.</creatorcontrib><creatorcontrib>Derby, Melissa</creatorcontrib><creatorcontrib>Martin, Dean F.</creatorcontrib><creatorcontrib>Wright, Scott D.</creatorcontrib><creatorcontrib>Dao, My Lien</creatorcontrib><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><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>International journal of toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Thomas K.</au><au>Derby, Melissa</au><au>Martin, Dean F.</au><au>Wright, Scott D.</au><au>Dao, My Lien</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Brevetoxins on Murine Myeloma SP2/O Cells: Aberrant Cellular Division</atitle><jtitle>International journal of toxicology</jtitle><addtitle>Int J Toxicol</addtitle><date>2003-03-01</date><risdate>2003</risdate><volume>22</volume><issue>2</issue><spage>73</spage><epage>80</epage><pages>73-80</pages><issn>1091-5818</issn><eissn>1092-874X</eissn><abstract>Massive deaths of manatees (Trichechus manatus latirostris) during the red tide seasons have been attributed to brevetoxins produced by the dinoflagellate Karenia brevis (formerly Ptychodiscus breve and Gymnodinium breve). Although these toxins have been found in macrophages and lymphocytes in the lung, liver, and secondary lymphoid tissues of these animals, the molecular mechanisms of brevetoxicosis have not yet been identified. To investigate the effects of brevetoxins on immune cells, a murine myeloma cell line (SP2/O) was used as a model for in vitro studies. By adding brevetoxins to cultures of the SP2/O cells at concentrations ranging from 20 to 600 ng/ml, an apparent increase in proliferation was observed at around 2 hours post challenge as compared to the unchallenged cell cultures. This was followed by a drop in cell number at around 3 hours, suggesting an aberrant effect of brevetoxins on cellular division, the cells generated at 2 hours being apparently short-lived. In situ immunochemical staining of the SP2/O cells at 1 and 2 hour post challenge showed an accumulation of the toxins in the nucleus. A 21-k Da protein was subsequently isolated from the SP2/O cells as having brevetoxin-binding properties, and immunologically identified as p21, a nuclear factor known to down-regulate cellular proliferation through inhibition of cyclindependent kinases. These data are the first on a possible effect of brevetoxins on the cell cycle via binding to p21, a phenomenon that needs to be further investigated and validated in normal immune cells.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>12745987</pmid><doi>10.1080/10915810305095</doi><tpages>8</tpages></addata></record> |
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subjects | Animal, plant and microbial ecology Animals Applied ecology Biological and medical sciences Blotting, Western Carrier Proteins - metabolism Cell Division - drug effects Cell Nucleus - drug effects Cell Nucleus - metabolism Cell Survival - drug effects Cyclin-Dependent Kinase Inhibitor p21 Cyclins - metabolism Dinoflagellida Dose-Response Relationship, Drug Ecotoxicology, biological effects of pollution Fundamental and applied biological sciences. Psychology Gymnodinium Immunohistochemistry Karenia brevis Marine and brackish environment Marine Toxins - immunology Marine Toxins - metabolism Marine Toxins - toxicity Medical sciences Mice Oxocins - immunology Oxocins - metabolism Oxocins - toxicity Plant poisons toxicology Plasmacytoma - pathology Ptychodiscus breve Toxicology Trichechus Trichechus manatus latirostris Tumor Cells, Cultured - drug effects Tumor Cells, Cultured - metabolism Tumor Cells, Cultured - pathology |
title | Effects of Brevetoxins on Murine Myeloma SP2/O Cells: Aberrant Cellular Division |
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