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A two-stage mouse skin carcinogenesis study of lyngbyatoxin A

  • H. Fujiki
  • M. Suganuma
  • H. Hakii
  • G. Bartolini
  • R. E. Moore
  • S. Takayama
  • T. Sugimura
Short Communication

Summary

A strong skin irritant, lyngbyatoxin A, isolated from the marine blue-green alga Lyngbya majuscula is structurally related to teleocidin. Since lyngbyatoxin A statisfied our short-term screening tests for possible tumor promoters, viz. irritation of mouse ear, induction of ornithine decarboxylase (ODC) in mouse skin, and adhesion of human promyelocytic leukemia cells (HL-60), a two-stage carcinogenesis experiment was carried out. Tumor incidences in the groups treated with 7,12-dimethylbenz(a)anthracene (DMBA) plus lyngbyatoxin A and with DMBA plus 12-O-tetradecanoylphorbol-13-acetate (TPA) were 86.7% and 93.3% in week 30, respectively. The average number of tumors per mouse was 3.7 in the former group and 10.5 in the latter group. This paper reports for the first time the potent tumor-promoting activity of lyngbyatoxin A and also the histological examination of tumors.

Key words

Lyngbyatoxin A Teleocidin New tumor promoter 

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References

  1. Cardellina JH II, Marner FJ, Moore RE (1979) Seaweed dermatitis: Structure of lyngbyatoxin A. Science 204:193–195Google Scholar
  2. Eliasson L, Kallin B, Patarroyo M, Klein G, Fujiki H, Sugimura T (1983) Activation of the the EBV-cycle and aggregation of human blood lymphocytes by tumor promoters teleocidin, lyngbyatoxin A, aplysiatoxin and debromoaplysiatoxin. Int J Cancer 31:7–11Google Scholar
  3. Fujiki H, Sugimura T (1984) New potent tumor promoters: teleocidin, lyngbyatoxin A and aplysiatoxin. In: Slaga T, Montesano R (eds) Cancer surveys. Vol 2. Oxford University Press, London pp 539–556Google Scholar
  4. Fujiki H, Mori M, Nakayasu M, Terada M, Sugimura T, Moore RE (1981) Indole alkaloids: dihydroteleocidin B teleocidin, and lyngbyatoxin A as members of a new class of tumor promoters. Proc Natl Acad Sci USA 78:3872–3876Google Scholar
  5. Fujiki H, Suganuma M, Matsukura N, Sugimura T, Takayama S (1982) Teleocidin from Streptomyces is a potent promoter of mouse skin carcinogenesis. Carcinogenesis 3:895–898Google Scholar
  6. Fujiki H, Sugimura T, Moore RE (1983a) New Classes of environmental tumor promoters: Indole alkaloids and polyacetates. Environ Health Perspect 50:85–90Google Scholar
  7. Fujiki H, Suganuma M, Moore RE, Sugimura T (1983b) New tumor promoters: dihydroteleocidin B, teleocidin, lyngbyatoxin A, aplysiatoxin and debromoaplysiatoxin. In: Harris CC, Autrup H (eds) Human carcinogenesis. Acadmic Press, New York, pp 303–324Google Scholar
  8. Fujiki H, Suganuma M, Tahira T, Yoshioka A, Nakayasu M, Endo Y, Shudo K, Takayama S, Moore RE, Sugimura T (1984a) New classes of tumor promoter: Teleocidin, aplysiatoxin and palytoxin. In: Fujiki H, Hecker E, Moore RE, Sugimura T, Weinstein IB (eds) Proceedings of the 14th International Symposium of the Princess Takamatsu Cancer Research Fund. Japan Scientific Societies Press, Tokyo (in press)Google Scholar
  9. Fujiki H, Tanaka Y, Miyake R, Kikkawa U, Nishizuka Y, Sugimura T (1984b) Activation of calcium-activated, phospholipid-dependent protein kinase (protein kinase C) by new classes of tumor promoters: teleocidin and debromoaplysiatoxin. Biochem Biophys Res Commun 120:339–343Google Scholar
  10. Moore RE (1981) Constituents of blue-green algae. In: Scheur PJ (ed) Marine natural products, vol IV. Academic Press, New York, pp 1–52Google Scholar
  11. Moore RE (1982) Toxins, anticancer agents, and tumor promoters from marine prokaryotes. Pure and Applied Chemistry 54:1919–1934Google Scholar
  12. Nakayasu M, Fujiki H, Mori M, Sugimura T, Moore RE (1981) Teleocidin, lyngbyatoxin A and their hydrogenated derivatives, possible tumor promoters, induce terminal differentiation in HL-60 cells. Cancer Lett 12:271–277Google Scholar
  13. Nishino H, Fujiki H, Terada M, Sato S (1983) Enhanced incorporation of radioactive inorganic phosphate into phospholipids of HeLa cells by tumor promoters. Carcinogenesis 4:107–110Google Scholar
  14. Sakamoto H, Terada M, Fujiki H, Mori M, Nakayasu M, Sugimura T, Weinstein IB (1981) Stimulation of prostaglandin production and choline turnover in HeLa cells by lyngbyatoxin A and dihydroteleocidin B. Biochem Biophys Res Commun 102: 100–107Google Scholar
  15. Schmidt R, Adolf W, Marton A, Roeser H, Sorg B, Fujiki H, Sugimra T, Moore RE, Hecker E (1983) Inhibition of specific binding of [3H]phorbol-12,13-dipropionate to an epidermal fraction by certain irritants and irritant promoters of mouse skin. Carcinogenesis 4:77–81Google Scholar
  16. Sugiumura (1982) Potent tumor promoters other than phorbol ester and their significance. Gann 73:499–507Google Scholar
  17. Sugimura T, Fujiki H (1983) Effect of tumor promoters in relation to the cell membrane. Gann Monogr 29:3–15Google Scholar
  18. Sugimura T, Fujiki H, Mori M, Nakayasu M, Terada M, Umezawa K, Moore RE (1982) Teleocidin: new naturally occurring tumor promoter. In: Hecker E, Fusenig NE, Kunz W, Marks F, Thielmann HW (eds) Carcinogenesis — A comprehensive survey. Raven Press, New York, pp 69–73Google Scholar
  19. Takashima M, Sakai H (1960) A new toxic substance, teleocidin, produced by Streptomyces. I. Production, isolation and chemical studies. Bull Arg Chem Soc Jpn 24:647–651Google Scholar
  20. Umezawa K, Weinstein IB, Horowitz A, Fujiki H, Matsushima T, Sugimura T (1981) Similarity of teleocidin B and phorbol ester tumor promoters in effects on membrane receptors. Nature 290:411–413Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • H. Fujiki
    • 1
  • M. Suganuma
    • 1
  • H. Hakii
    • 1
  • G. Bartolini
    • 2
  • R. E. Moore
    • 2
  • S. Takayama
    • 3
  • T. Sugimura
    • 1
  1. 1.National Cancer Center Research InstituteChuo-ku, TokyoJapan
  2. 2.Department of ChemistryUniversity of HawaiiHonoluluUSA
  3. 3.Department of Experimental PathologyCancer InstituteToshima-ku, TokyoJapan

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