Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR

  • Rie Nishiwaki-Matsushima
  • Tetsuya Ohta
  • Shinji Nishiwaki
  • Masami Suganuma
  • Kiyomi Kohyama
  • Takatoshi Ishikawa
  • Wayne W. Carmichael
  • Hirota Fujiki
Original Papers Experimental Oncology


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.

Key words

Microcystin Tumor promoter Protein phosphatase 







glutathioneS-transferase placental form


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Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Rie Nishiwaki-Matsushima
    • 1
  • Tetsuya Ohta
    • 1
  • Shinji Nishiwaki
    • 1
  • Masami Suganuma
    • 1
  • Kiyomi Kohyama
    • 2
  • Takatoshi Ishikawa
    • 3
  • Wayne W. Carmichael
    • 4
  • Hirota Fujiki
    • 1
  1. 1.Cancer Prevention DivisionNational Cancer Center Research InstituteTokyoJapan
  2. 2.Department of Experimental PathologyCancer InstituteTokyoJapan
  3. 3.Department of Pathology, Faculty of MedicineTokyo UniversityTokyoJapan
  4. 4.Department of Biological SciencesWright State UniversityDaytonUSA

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