This Academic Research Enhancement Award (AREA, R15) application proposes to test the hypothesis that lycopene, a carotenoid which is not converted to vitamin A, is effective in suppressing chemically induced colon cancer in the rat. In experiment 1, the optimal concentration of dietarily administered lycopene-rich tomato extract that inhibits chemically-induced aberrant crypt foci formation will be determined. Groups of 10 Fisher 344 male rats will be fed various concentrations of lycopene-rich tomato extract (0, 0.1, 0.2, 0.4, 0.8, and 1.6 mMoles/kg) for 13 weeks. At weeks 7 and 8, the rats will be given two sc injections of azoxymethane in saline (16 mg/kg body weight). Rats will be sacrificed at 17 weeks of age and aberrant crypt foci in distal and proximal colon counted. In experiment 2, 60 rats will be assigned to four diets in 2 x 2 factorial arrangement with two levels of fat (7% and 21%) and two lycopene levels (0% and a to-be-determined concentration from experiment 1). In addition to aberrant crypt foci counts, measurement of glutathione-s-transferase, ornithine decarboxylase, and ras-p21 will be conducted on colonic mucosa.
