Protective effects of ellagic acid and other plant phenols on benzo[a]pyrene-induced neoplasia in mice

Abstract

The inhibitory effects of three phenolic compounds (ferulic, chlorogenic and ellagic acids) on benzo[a]pyrene- and 7,12-dimethylbenz[a]anthracene-induced neoplasia have been investigated in mice. Ellagic acid was the most potent antagonist of tumorigenesis since this compound is active, by i.p. administration or added in the diet, on benzo[a]pyrene-induced pulmonary adenoma formation in A/J mice and, after topical application, on 7,12-dimethylbenz[a]anthracene-induced skin tumorigenesis in NMRI Swiss mice. If ellagic acid has little or no effect on the number of tumor bearing animals, the incidence of pulmonary tumors per animal is decreased by greater than 50%. Ferulic acid and chlorogenic acid (5 X 100 mg/kg, by i.p. route) were also active, but less than ellagic acid, against the lung carcinogenesis by benzo[a]-pyrene (100 mg/kg, i.p.) but were totally ineffective against the formation of skin tumors by 7,12-dimethylbenz[a]anthracene. These results remarkably paralleled the in vitro antimutagenic effects of these compounds shown by Wood et al. on benzo[a]pyrene. It must be noted that ellagic acid only exerted, by i.p. route, a severe toxicity after four injections of 100 mg/kg, in oil suspension, whereas the oral administration in the diet (a daily dose of 100 mg/kg during 15 days) did not cause any toxicity.