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 agents of 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mammary gland carcinogenesis, were examined as potential post-initiation suppressing agents. Treatment 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:corn oil (2:3) (2.5 ml/kg b.w.), three times weekly by gavage, started 3 weeks after the initiation with 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 significantly in the overall outcome of mammary tumorigenesis including cumulative mammary tumor incidences and multiplicities, latent periods and number and weight of mammary tumors per tumor-bearing rat for malignant, benign and/or malignant + benign tumors. A tendency of the I3C-treated rats to develop fewer mammary adenocarcinomas with a greater average weight per tumor per 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 I3C on tumor development and growth. A 12-week treatment with I3C or beta-NF significantly increased the P450-dependent activities of ethoxy-, methoxy-, benzyloxy- and pentoxy-(with I3C only) resorufin O-dealkylase in hepatic microsomes indicating induction of several P450s. The alterations in the P450 complement may affect endogenous estrogen metabolism and mammary gland and tumor characteristics at the molecular level, e.g. estrogen receptor status and/or proliferative activity, which require further studies.
Malejka-Giganti
D
D
Veterans Affairs Medical Center (151), One Veterans Drive, Minneapolis, MN 55417-2300, USA. malej001@maroon.tc.umn.edu
Niehans
G A
GA
Reichert
M A
MA
Bliss
R L
RL
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D004334:Drug Administration Schedule; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019324:beta-Naphthoflavone / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D007211:Indoles; D007527:Isoenzymes; D015127:9,10-Dimethyl-1,2-benzanthracene; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; C016517:indole-3-carbinol