Phorbol diacetate inhibits superoxide anion radical production and tumor promotion by mezerein

The ability of the non-promoter phorbol diacetate (PDA) to modulate superoxide anion radical production by the complete tumor promoter phorbol myristate acetate (PMA) or the second stage promoter mezerein was assessed. Superoxide anion radical production was measured by the superoxide dismutase inhi...

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Bibliographic Details
Published inCarcinogenesis (New York) Vol. 7; no. 10; p. 1637
Main Authors Czerniecki, B, Gad, S C, Reilly, C, Smith, A C, Witz, G
Format Journal Article
LanguageEnglish
Published England 01.10.1986
Subjects
Animals
Carcinogens
Diterpenes
Female
Free Radicals
Hyperplasia
Macrophages - metabolism
Mice
Phorbol Esters - pharmacology
Skin - pathology
Skin Neoplasms - chemically induced
Skin Neoplasms - prevention & control
Superoxides - metabolism
Terpenes - toxicity
Tetradecanoylphorbol Acetate
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Summary:The ability of the non-promoter phorbol diacetate (PDA) to modulate superoxide anion radical production by the complete tumor promoter phorbol myristate acetate (PMA) or the second stage promoter mezerein was assessed. Superoxide anion radical production was measured by the superoxide dismutase inhibitable reduction of nitroblue tetrazolium (NBT) to a blue intracellular formazan precipitate. These studies demonstrated that superoxide anion radical production by murine peritoneal exudate cells (PEC) stimulated by i.p. injection with mezerein (100 ng) is inhibited in a dose-dependent manner by co-administration with PDA (1-1000 ng). There was no effect on the number of formazan-positive PEC when PDA was co-administered with PMA. In a two-stage tumor promotion bioassay in female SENCAR mice initiated with 25.6 micrograms dimethylbenz[a]anthracene (DMBA) followed by first stage promotion with PMA (4X, 2 micrograms), co-administration of mezerein (2 micrograms) with 2 micrograms or 20 micrograms PDA reduced the number of papillomas after 14 weeks by 38% and 44%, respectively, compared with mezerein treatment alone. PDA (20 micrograms) when co-administered with mezerein (2 micrograms) does not inhibit mezerein induced hyperplasia in mouse skin. These results suggest a correlation between the ability of PDA to inhibit both superoxide anion radical production and tumor promotion by mezerein.
ISSN:0143-3334
DOI:10.1093/carcin/7.10.1637