The abilities of
5,6-benzoflavone (5,6-BF, a synthetic
flavonoid),
indole-3-carbinol (I3C, a plant derived product) or
diindolylmethane (DIM, a condensation product of I3C) to alter the induction of
mammary cancers induced by the
carcinogens 7,12-dimethylbenzanthracene (DMBA) or
N-methyl-N-nitrosourea (MNU) were evaluated. Interestingly, the first two agents act as
aryl hydrocarbon receptor (AhR) agonists, while DIM does not. The agents were initially examined for their ability to inhibit DMBA-induced mammary
carcinogenesis. Agents were administered for 14 days starting 7 days prior to a single dose of the
carcinogen. Evaluated over an extensive range of doses (165, 550 and 1650 ppm in the diet), 5,6-BF caused a dose-dependent decrease of
mammary cancers. In addition, 5,6-BF at doses of 1650 and 165 ppm in the diet blocked the induction of DMBA-induced
DNA adducts in the mammary gland by approximately 85% and 45%, respectively. In contrast, DIM (180 or 20 mg/kg BW/day) failed to block induction of DMBA
tumors. The effect of these agents on the promotion/progression phase of
carcinogenesis using the MNU
mammary cancer model was also determined. 5,6-BF (1650 or 165 ppm in the diet), I3C (180 or 60 mg/kg BW/day administered by gavage), or DIM (180 or 60 mg/kg BW/day by gavage) were initiated 5 days after the administration of MNU, and continually thereafter. 5,6-BF decreased MNU- induced mammary
tumor multiplicity by 40-60%. I3C reduced
tumor multiplicity at the high dose, while DIM at either dose had minimal effects on
tumor multiplicity. Thus, 5,6-BF and I3C were highly effective against initiation of DMBA-induced mammary
carcinogenesis, and were also effective against MNU-induced
tumors during the promotion/progression phase of
carcinogenesis. In contrast, DIM had minimal effects in either model; arguing that administration of DIM is not analogous to administration of I3C.