EFFICACY STUDIES OF CHEMOPREVENTIVE AGENTS

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The efficacy of a variety of chemopreventive agents to reduce or inhibit colon cancer using male Fisher 344 rats is being studied. Aberrant crypt formation is being measured four weeks after the first carcinogen exposure, according to methods of Tudek, Bird, and Bruce (Cancer Research 49:1236-1240, 1989). The rats are being standard semi-purified AIN-76A diet and given two injections of 15 mg of azoxymethane (AOM) per kg of body weight one week apart. The test chemopreventive agent are given to the rats from one week prior to and four weeks following the first carcinogen treatment. Then kill the rats and score the aberrant crypts (see Bird, Cancer Lett.37:147-151, 1987). 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 scored under light microscopy. All groups are coded and groups are scored in a blinded manner by two independent scorers. Perform an appropriate statistical analysis on all data to determine significance of enhancing or inhibiting effects of the various agents. The classes of agent being studied include lipoxyganse Inhibitors, INOS inhibitors, newer antiinflammatory agents and combinations of these and other agents.