Protective effects against liver, colon, and tongue carcinogenesis by plant phenols

Three different experiments were performed in order to examine the potential inhibitory effects of the plant phenolic compounds ellagic acid (EA) and chlorogenic acid (CA) on chemical carcinogenesis. Experiment I: The effect of dietary EA (400 ppm for 18 weeks) on the carcinogenicity to rats of concurrently administered N-2-fluorenylacetamide (FAA, 200 ppm in diet for 16 weeks) was determined. Experiment II: The effect of EA in diet (400 ppm for 10 weeks) on the rat tongue carcinogenesis by 4-nitroquinoline 1-oxide (4-NQO, 10 ppm in drinking water for 8 weeks) during the initiation stage was investigated. Experiment III: The protective effect of dietary CA (250 ppm for 24 weeks) on methylazoxymethanol (MAM) acetate (a single i.v. injection, 20 mg./kg body weight)-induced colon and liver carcinogenesis during the post-initiation stage was examined in Syrian golden hamsters. In the rats receiving EA together with FAA or 4-NQO, the incidence of neoplasm in the liver (30%) or tongue (20X) was significantly decreased compared with those of rats given the carcinogen alone (100% in liver; 71% in tongue). Similarly, colon tumor (13X) and liver cell foci (6.0 +/- 2.7/cm2) incidence in hamsters given MAM acetate and CA was significantly smaller than those of hamsters given MAM acetate alone (50% and 10.8 +/- 2.7/cm2). These results suggest that the plant phenolics EA and CA are potential chemopreventive agents in carcinogenesis. The number and area of AgNORs in epithelial cell nuclei of liver, tongue, and colon of animals were also quantified in order to evaluate the proliferative activity of cells. The number and area of AgNORs of nuclei of the target organs from the animals treated with the carcinogens and test chemicals were significantly lower than those of animals given the carcinogen alone, indicating that EA and CA suppressed the proliferative activity of targeted epithelial cells and AgNOR enumeration could be a useful method for estimating the chemopreventive potential of certain chemicals in carcinogenesis.