Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR
Certain waterblooms of toxic cyanobacteria (blue-green algae) are a health threat because of their production of toxic peptides, termed microcystins, which cause liver damage in wild and domesticated animals. The most widely studied microcystin is microcystin-LR, a heptapeptide containing the two L-...
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Veröffentlicht in: | Journal of cancer research and clinical oncology 1992-06, Vol.118 (6), p.420-424 |
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creator | NISHIWAKI-MATSUHIMA, R OHTA, T NISHIWAKI, S SUGANUMA, M KOHYAMA, K ISHIJKAWA, T CARMICHAEL, W. W FUJIKI, H |
description | Certain waterblooms of toxic cyanobacteria (blue-green algae) are a health threat because of their production of toxic peptides, termed microcystins, which cause liver damage in wild and domesticated animals. The most widely studied microcystin is microcystin-LR, a heptapeptide containing the two L-amino acids, leucine and arginine. The inhibition of protein phosphatase type 1 and type 2A activities by microcystin-LR is similar to that of the known protein phosphatase inhibitor and tumor promoter okadaic acid. We show in this report that microcystin-LR, applied below the acute toxicity level, dose-dependently increases the number and percentage area of positive foci for the placental form of glutathione S-transferase in rat liver, which was initiated with diethylnitrosamine. The result was obtained independently through two animal experiments. This observation indicates that microcystin-LR is a new liver tumor promoter mediated through inhibition of protein phosphatase type 1 and type 2A activities. This provides further evidence that the okadaic acid pathway is a general mechanism of tumor promotion in various organs, such as mouse skin, rat glandular stomach and rat liver. |
doi_str_mv | 10.1007/bf01629424 |
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The result was obtained independently through two animal experiments. This observation indicates that microcystin-LR is a new liver tumor promoter mediated through inhibition of protein phosphatase type 1 and type 2A activities. This provides further evidence that the okadaic acid pathway is a general mechanism of tumor promotion in various organs, such as mouse skin, rat glandular stomach and rat liver.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/bf01629424</identifier><identifier>PMID: 1618889</identifier><identifier>CODEN: JCROD7</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Alanine Transaminase - blood ; Animals ; Aspartate Aminotransferases - blood ; Biological and medical sciences ; Biomarkers, Tumor - analysis ; Carcinogenesis, carcinogens and anticarcinogens ; Chemical agents ; Cyanobacteria ; Diethylnitrosamine - toxicity ; Glutathione Transferase - analysis ; Liver Neoplasms - chemically induced ; Liver Neoplasms - enzymology ; Liver Neoplasms - pathology ; Male ; Marine Toxins - toxicity ; Medical sciences ; Microcystins ; Peptides, Cyclic - toxicity ; Phenobarbital - toxicity ; Rats ; Rats, Inbred F344 ; Tumors</subject><ispartof>Journal of cancer research and clinical oncology, 1992-06, Vol.118 (6), p.420-424</ispartof><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-442e5fb5bbc636d0067ff4bcae8c7d87e3bb3806d6c28e9e3a6a15de8798dcae3</citedby><cites>FETCH-LOGICAL-c377t-442e5fb5bbc636d0067ff4bcae8c7d87e3bb3806d6c28e9e3a6a15de8798dcae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5582159$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1618889$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>NISHIWAKI-MATSUHIMA, R</creatorcontrib><creatorcontrib>OHTA, T</creatorcontrib><creatorcontrib>NISHIWAKI, S</creatorcontrib><creatorcontrib>SUGANUMA, M</creatorcontrib><creatorcontrib>KOHYAMA, K</creatorcontrib><creatorcontrib>ISHIJKAWA, T</creatorcontrib><creatorcontrib>CARMICHAEL, W. W</creatorcontrib><creatorcontrib>FUJIKI, H</creatorcontrib><title>Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR</title><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><description>Certain waterblooms of toxic cyanobacteria (blue-green algae) are a health threat because of their production of toxic peptides, termed microcystins, which cause liver damage in wild and domesticated animals. The most widely studied microcystin is microcystin-LR, a heptapeptide containing the two L-amino acids, leucine and arginine. The inhibition of protein phosphatase type 1 and type 2A activities by microcystin-LR is similar to that of the known protein phosphatase inhibitor and tumor promoter okadaic acid. We show in this report that microcystin-LR, applied below the acute toxicity level, dose-dependently increases the number and percentage area of positive foci for the placental form of glutathione S-transferase in rat liver, which was initiated with diethylnitrosamine. The result was obtained independently through two animal experiments. This observation indicates that microcystin-LR is a new liver tumor promoter mediated through inhibition of protein phosphatase type 1 and type 2A activities. This provides further evidence that the okadaic acid pathway is a general mechanism of tumor promotion in various organs, such as mouse skin, rat glandular stomach and rat liver.</description><subject>Alanine Transaminase - blood</subject><subject>Animals</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>Chemical agents</subject><subject>Cyanobacteria</subject><subject>Diethylnitrosamine - toxicity</subject><subject>Glutathione Transferase - analysis</subject><subject>Liver Neoplasms - chemically induced</subject><subject>Liver Neoplasms - enzymology</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Marine Toxins - toxicity</subject><subject>Medical sciences</subject><subject>Microcystins</subject><subject>Peptides, Cyclic - toxicity</subject><subject>Phenobarbital - toxicity</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Tumors</subject><issn>0171-5216</issn><issn>1432-1335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtLxDAUhYMo4zi6cS9k4Uqo5tE8utTBUaEwILoueWKkL5Io9t9bmVFXl8P5OBc-AM4xusYIiRvtEeakKkl5AJa4pKTAlLJDsERY4IIRzI_BSUrvaM5MkAVYYI6llNUSbOvw6SLMH90Q4RiHbshh6KGeYH5z0EyqH7Qy2cWg2jmaNhg4ujEH62AevkIPu2DiYKaUQ1_Uz6fgyKs2ubP9XYHXzf3L-rGotw9P69u6MFSIXJQlccxrprXhlFuEuPC-1EY5aYSVwlGtqUTcckOkqxxVXGFmnRSVtDNFV-Bqtzs_Tyk634wxdCpODUbNj5TmbvMrZYYvdvD4oTtn_9Gdhbm_3PcqGdX6qHoT0h_GmCSYVfQbcsRqvg</recordid><startdate>19920601</startdate><enddate>19920601</enddate><creator>NISHIWAKI-MATSUHIMA, R</creator><creator>OHTA, T</creator><creator>NISHIWAKI, S</creator><creator>SUGANUMA, M</creator><creator>KOHYAMA, K</creator><creator>ISHIJKAWA, T</creator><creator>CARMICHAEL, W. 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W</au><au>FUJIKI, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR</atitle><jtitle>Journal of cancer research and clinical oncology</jtitle><addtitle>J Cancer Res Clin Oncol</addtitle><date>1992-06-01</date><risdate>1992</risdate><volume>118</volume><issue>6</issue><spage>420</spage><epage>424</epage><pages>420-424</pages><issn>0171-5216</issn><eissn>1432-1335</eissn><coden>JCROD7</coden><abstract>Certain waterblooms of toxic cyanobacteria (blue-green algae) are a health threat because of their production of toxic peptides, termed microcystins, which cause liver damage in wild and domesticated animals. The most widely studied microcystin is microcystin-LR, a heptapeptide containing the two L-amino acids, leucine and arginine. The inhibition of protein phosphatase type 1 and type 2A activities by microcystin-LR is similar to that of the known protein phosphatase inhibitor and tumor promoter okadaic acid. We show in this report that microcystin-LR, applied below the acute toxicity level, dose-dependently increases the number and percentage area of positive foci for the placental form of glutathione S-transferase in rat liver, which was initiated with diethylnitrosamine. The result was obtained independently through two animal experiments. This observation indicates that microcystin-LR is a new liver tumor promoter mediated through inhibition of protein phosphatase type 1 and type 2A activities. This provides further evidence that the okadaic acid pathway is a general mechanism of tumor promotion in various organs, such as mouse skin, rat glandular stomach and rat liver.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>1618889</pmid><doi>10.1007/bf01629424</doi><tpages>5</tpages></addata></record> |
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subjects | Alanine Transaminase - blood Animals Aspartate Aminotransferases - blood Biological and medical sciences Biomarkers, Tumor - analysis Carcinogenesis, carcinogens and anticarcinogens Chemical agents Cyanobacteria Diethylnitrosamine - toxicity Glutathione Transferase - analysis Liver Neoplasms - chemically induced Liver Neoplasms - enzymology Liver Neoplasms - pathology Male Marine Toxins - toxicity Medical sciences Microcystins Peptides, Cyclic - toxicity Phenobarbital - toxicity Rats Rats, Inbred F344 Tumors |
title | Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR |
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