Expression of Metabolic and Apoptotic Genes During Treatment With Chemopreventive Agents for Breast Cancer

摘要

Two studies related to breast cancer prevention were conducted: (1) The effects of treatment of femaile Sprague-Dawley rats with indole-3-carbinol (I3C), tamoxifen (TAM) or TAM+I3C on caspase activities in the mammary gland and mammary tumors induced with 7,12-dimethylbenz(alpha)anthracene (DMBA). Activities of caspase-3+7,-6 and -9 in the mammary gland of tumor-free DMBA- initiated rats were up-regulated by a 14 to 58 treatments with I3C. DMBA initiation was found to reduce the activities of caspase-3+7 and -8 in the mammary gland: (2) The effects of treatment of rats with 3,3'-diindolylmethane (DIM), the dimmer of I3C formed in gastric acid, on the gene expression level of hepatic cytochrome P450s (CYPs) involved in estrogen metabolism. The results indicated that treatment with Phenobarbital (PB), a relevant inducer, increased mRNA expression of CYP2B1/2 significantly and 3A1.2 insignificantly, and treatment with DIM insignificantly up-regulated hepatic mRNA levels of CYP1A1 and 2B1/2. When combined with PB, treatment with DIM significantly induced mRNA level of CYP1A1, and at low does level of DIM, CYP2B1, and 3A2. These two studies suggested the prevention of mammary tumorigenesis by 13C and DIM may be explained by their effects on apoptosis and estrogen metabolism.