Expression of Metabolic and Apoptotic Genes During Treatment With Chemopreventive Agents With Breast Cancer
Abstract
Metabolic and apoptotic genes underlying the effects of indole-3-carbinol (I3C) on breast cancer chemoprevetion were examined. A short-term (up to 10 days) treatment of rats with I3C at 5 or 25 mg/kg b.wt. ahs bee found to induce activities of caspase-3, -8, and -9 in the mammary gland, and at 250 mg/kg, upregulate the mRNA transcriptions of hepatic CYP1A1, 1B1, and 2B1/2 and mammary CYP1A1, and the oxidateive metabolism of 17b-estradiol and estrone by liver microsomes. Further, postcarcinogen treatment (thrice weekly for up to 20 weeks) of rats with tamoxifen (TAM) (10 microg/rat), I3C (250 mg/kg b.wt.) or TAM+I3C showed that the latency of malignant mammary tumors was significantly increased from 70 to 112 days in TAM- or TAM+I3C-treated rats compared to vehicle- or I3C treated rats. The mean number of malignant mammary tumors per rat was significantly decreased in the TAM-, I3C- or TAM+I3C-treated groups, and the mean tumor mass per rat was decreased in TAM-or TAM+I3C-treated groups. The data indicate that treatment with relatively low doses of TAM effectively suppresses mammary trumorigenesis, and TAM and I3C elicit cooperative effects in suppression of mammary tumor multiplicity. The mechanisms underlying the suppressing effects of I3C may vary at different dose levels.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA424662
Entities
People
- Yongjian Lu
Organizations
- University of Minnesota