Chemoprevention of Azoxymthane - Induced Foci of Aberrant Crypts in Colons of Rats Treated with Chemopreventive Agents. The efficacy of a variety of chemopreventive agents to reduce or inhibit colon cancer using male Fisher 344 rats treated with a carcinogen + - chemopreventive agents is being assessed. Aberrant crypt formation four weeks after the first carcinogen exposure is being measured according to methods of Tudek, Bird, and Bruce (Cancer Research 49:1236-1240, 1989). All rats, approximately 8 weeks old, are treated with two injections of 15 mg of azoxymethane (AOM) per kg of body weight one week apart. An dose selection study is performed prior to the chemoprevention study for each agent at five doses. For Protocol A: Administer each agent at five doses to approximately seven-week-old rats. Feed the rats the test chemopreventive agent from one week prior to and four seeks following the first carcinogen treatment. Then kill the rats and score the aberrant crypts (see Bird, Cancer Lett.37:147-151, 1987). For Protocol B: Administration of the chemopreventive agents shall begin 4 weeks after the first carcinogen dose and continued for four weeks. At eight weeks following the first carcinogen treatment aberrant crypts will be scored. For both protocols, the number of aberrant crypt foci per colon and the number of aberrant crypts per foci from unsectioned methylene-blue stained colons are being determined. The two doses to be used in the aberrant crypt foci study are determined from data produced in the rangefinding assay and obtain approval from the Project Officer. Ten animals are being used per group. There are 20 agents in protocol A and 10 in protocol B.
| Swamy, Malisetty V; Cooma, Indranie; Reddy, Bandaru S et al. (2002) Lamin B, caspase-3 activity, and apoptosis induction by a combination of HMG-CoA reductase inhibitor and COX-2 inhibitors: a novel approach in developing effective chemopreventive regimens. Int J Oncol 20:753-9 |
| Steele, Vernon E; Boone, Charles W; Dauzonne, Daniel et al. (2002) Correlation between electron-donating ability of a series of 3-nitroflavones and their efficacy to inhibit the onset and progression of aberrant crypt foci in the rat colon. Cancer Res 62:6506-9 |
