Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR |
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Authors: | Rie Nishiwaki-Matsushima Tetsuya Ohta Shinji Nishiwaki Masami Suganuma Kiyomi Kohyama Takatoshi Ishikawa Wayne W. Carmichael Hirota Fujiki |
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Affiliation: | (1) Cancer Prevention Division, National Cancer Center Research Institute, 104 Tokyo, Japan;(2) Department of Experimental Pathology, Cancer Institute, 170 Tokyo, Japan;(3) Department of Pathology, Faculty of Medicine, Tokyo University, 113 Tokyo, Japan;(4) Department of Biological Sciences, Wright State University, 45435 Dayton, OH, USA |
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Abstract: | Summary 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 twol-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 glutathioneS-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.Abbreviations DEN diethylnitrosamine - DMBA 7,12-dimethylbenz[a]anthracene - GST-P glutathioneS-transferase placental form |
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Keywords: | Microcystin Tumor promoter Protein phosphatase |
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