Post-initiation treatment of rats with indole-3-carbinol or beta-naphthoflavone does not suppress 7,12-dimethylbenz[a]anthracene-induced mammary gland carcinogenesis

Indole-3-carbinol (I3C) and beta -naphthoflavone (beta -NF), blocking agent s of 7,12-dimethylbenz[a]anthracene (DMBA)initiated mammary gland carcinoge nesis, were examined as potential post-initiation suppressing agents. Treat ment of female Sprague-Dawley rats with I3C (250 mg/kg body weight (b.w.)), beta -NF (20 mg/kg b.w.) or the vehicle ethanol:com oil (2:3) (2.5 ml/kg b .w.): three times weekly by gavage, started 3 weeks after the initiation wi th one oral dose of DMBA (20 mg/rat at 7 weeks of age) and continued for up to 12 weeks. I3C- or beta -NF- or vehicle-treated groups did not differ si gnificantly in the overall outcome of mammary tumorigenesis including cumul ative mammary tumor incidences and multiplicities, latent periods and numbe r and weight of mammary tumors per tumor-bearing rat for malignant, benign and/or malignant + benign tumors. A tendency of the I3C-tnated mts to devel op fewer mammary adenocarcinomas with a greater average weight per tumor pe r rat (2.32 +/- 1.50 g) than in the beta -NF- (1.52 +/- 1.58 g) or vehicle- (1.55 +/- 1.53 g) treated groups suggests an effect, yet to be confirmed, of 13C on tumor development and growth. A 12-week treatment with I3C or bet a -NF significantly increased the P450-dependent activities of ethoxy-, met hoxy-, benzyloxy- and pentoxy-(with I3C only) resorufin O-dealkylase in hep atic microsomes indicating induction of several P450s. The alterations in t he P450 complement may affect endogenous estrogen metabolism and mammary gl and and tumor characteristics at the molecular level, e.g. estrogen recepto r status and/or proliferative activity, which require further studies. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.