Suppressive effects of chlorogenic acid on N-methyl-N-nitrosourea-induced glandular stomach carcinogenesis in male F344 rats.

The modifying effects of chlorogenic acid (CA) on N-methyl-N-nitrosourea (MNU)-induced glandular stomach carcinogenesis were investigated in five groups of male F344 rats. Rats in Groups 1 through 3 were given MNU in drinking water at a concentration of 400 ppm for 12 weeks. Animals of Group 1 were then kept on the basal diet alone, and those of Group 2 or 3 were fed a diet containing 500 or 250 ppm CA for a subsequent 22 weeks. Group 4 was exposed to CA alone through the experimental period (36 weeks), and Group 5 was given the basal diet continuously and treated as a control. At the end of the experiment, the incidence of glandular stomach carcinoma of Group 3 was significantly smaller than that of Group 1 (p < 0.03). The incidence of adenomatous hyperplasia of Group 2 was also significantly lower than that of Group 1 (p < 0.02). In addition, the proliferating cell nuclear antigen (PCNA) labeling index of the epithelial cells from the non-neoplastic mucosa in rats of Group 2 or 3 was significantly smaller than that of Group 1 (p < 0.0001). These results suggest that CA has a chemopreventive effect on MNU-induced rat glandular stomach carcinogenesis by exposure during the post-initiation phase, and CA may be a promising agent for prevention of human stomach cancer.