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

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Abstract
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 dis-mutase inhibitable reduction of nitroblue tetrazolium (NBT) to a blue intracelhilar 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 fonnazan-positive PEC when PDA was co-administered with PMA. In a two-stage tumor promotion bioassay in female SENCAR mice initiated with 25.6 μ dimeihylbenz[a]anthracene (DMBA) followed by first stage promotion with PMA (4× 2 μg), co-administration of mezerein (2 μg) with 2 μg or 20 μg PDA reduced the number of papillomas after 14 weeks by 38% and 44%, respectively, compared with mezerein treatment alone. PDA (20 μg) when co-administered with mezerein (2 μig) 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.