Anti-mutagenesis and anti-promotion by apigenin, robinetin and indole-3-carbinol

We assessed the anti-mutagenic and anti-promotion properties of two flavones, apigenin and robinetin, and of indole-3-carbinol, because these compounds have been reported in vegetables, the consumption of which has been associated with reduced rates of cancer. However, the active components of these foods and their effects on carcinogenesis have not been established. Anti-mutagenicity was determined in the Salmonella typhimurium assay by measuring the effects of the test compounds on bacterial mutagenesis induced by methyl-nitrosourea (MNU), methyl-n-nitro-N-nitrosoguanidine (MNNG), benzo[a]pyrene (BaP) or 2-aminoanthracene (2-AA). Inclusion of apigenin resulted in a 62% and a 43% inhibition of mutagenicity with 13 nmol of 2-AA and 30 nmol BaP respectively. Robinetin caused an 87% inhibition of mutagenicity by 2-AA, but indole-3-carbinol had little or no effect on the mutagenicity of any of the compounds. None of the three compounds inhibited mutagenesis by MNU or MNNG and none were mutagenic or toxic when tested in the absence of mutagenic compounds at doses up to 20 micrograms/plate. Anti-promotion properties were assessed by measuring the effects of apigenin, robinetin and indole-3-carbinol on induction of ornithine decarboxylase activity (ODC) in mouse epidermis by 17 nmol 12-O-tetradecanoyl phorbol-13-acetate (TPA). Pretreatment of the skin half an hour before TPA with apigenin, robinetin, butylated hydroxyanisole, 13-cis-retinoic acid (all at 50 mumol) or di-fluoromethylornithine (1.6 mumol) inhibited ODC induction at 6 h after TPA by 67-80%. Pretreatment with 50 mumol indole-3-carbinol caused a 78% elevation in the TPA induction at this time. Dose response measurements were conducted with apigenin, indole-3-carbinol and robinetin. Inhibition by 30-90% of TPA-induced ODC was observed at 6 h after TPA in mice pretreated with 12.5-100 mumol apigenin. Pretreatment with 37.5 or 50 mumol indole-3-carbinol or 0.5, 12.5 or 25 mumol robinetin resulted in elevated induction of epidermal ODC by TPA at 6 h after TPA. However, treatment with 50 or 100 mumol robinetin diminished ODC induction at 6 h after TPA. Treatment with 100 mumol apigenin or 50 or 100 mumol indole-3-carbinol in non-TPA-treated mouse skin caused elevations in epidermal ODC. In comparing the time course of ODC induction, indole-3-carbinol (50 mumol) pretreatment shifted the induction of epidermal ODC to earlier times, in addition to elevating ODC induction by TPA.(ABSTRACT TRUNCATED AT 400 WORDS)