Polyamine biosynthesis and skin tumor promotion: Inhibition of 12-0-tetradecanoylphorbol-13-acetate-promoted mouse skin tumor formation by the irreversible inhibitor of ornithine decarboxylase α-difluoromethylornithine

Masaharu Takigawa, Ajit K. Verma, R. C. Simsiman, R. K. Boutwell

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)

Abstract

Application of 12-0-tetradecanoylphorbol-13-acetate (TPA) to mouse skin leads to the induction of ornithine decarboxylase (EC 4.1.1.17) and the accumulation of putrescine. The relevance of these TPA-induced changes to the mechanism of tumor promotion was determined using α-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase. α-Difluoromethylornithine applied to the skin of mice or administered in drinking water in conjunction with applications of TPA to 7,12-dimethylbenz[a]anthracene-initiated mouse skin inhibited the formation of mouse skin papillomas by 50 and 90% respectively; TPA-induced ornithine decarboxylase activity and the accumulation of putrescine were almost completely inhibited.

Original languageEnglish
Pages (from-to)969-976
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume105
Issue number3
DOIs
Publication statusPublished - Apr 14 1982
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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