Expression of Metabolic and Apoptotic Genes During Treatment With Chemopreventive Agents for Breast Cancer
Abstract
Effects of short-term (up to 2 weeks) treatment of rats with indole-3-carbinol (130) at three dose levels on mRNA expression of cytochrome P450 (CYP) in the liver and mammary gland and apoptotic activity in the mammary gland were examined. The mRNA transcripts for hepatic CYPlAl, lEl, and 2Bl/2 and mammary CYPlAl were upregulated after treatment with 130 at 250 mg/kg of body weight. This treatment also increased the oxidative metabolism of 17(3-estradiol (E2) and estrone (El) by liver microsomes. In the mammary gland, activities of caspase-3, -8, and -9 were induced by 130 at lower dose levels (5 mg/kg for 4-dose and 25 mg/kg for 10-dose treatment) . These results show that treatment with 130 at the high dose level altered the CYP complement and metabolite composition from E2 and El, and that at the lower dose levels induced apoptosis in tumor-target organ. The data suggest that mechanism(s) of induction of apoptosis by 130 does not involve modulation of P450- dependent estrogen mechanism. Likewise, apoptotic activity was not induced in mammary tumors (adenocarcinomas) during post-carcinogen treatment of rats with 13C at 250 mg/kg (24 to 36 doses during 8-12 weeks) . The level of apoptosis in mammary tumors was independent of treatment and likely reflected the intrinsic process of tumor apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408094
Entities
People
- Xuexian Zhang
Organizations
- University of Minnesota