EFFECTS OF CAFFEINE ON GLANDULAR STOMACH CARCINOGENESIS INDUCED IN RATS BY N-METHYL-N'-NITRO-N-NITROSOGUANIDINE AND SODIUM-CHLORIDE

The modifying effects of caffeine ingestion on glandular stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride (NaCl) were investigated in male Wistar rats. Animals were given a MNNG solution (100 ppm) as their drinking water and simultaneously fed a diet supplemented with 5% NaCl for 8 wk. They then received 0.25% caffeine solution (groups 1 and 3) or tap water (groups 2 and 4) as the drinking water, and were fed the NaCl diet (groups 1 and 2) or basal diet (groups 3 and 4) for the following 32 wk. Both caffeine and NaCl treatments exerted growth retardation effects, the suppression being stronger with caffeine than NaCl, and animals in group 1 (NaCl plus caffeine) showing the lowest body weight. The incidence of adenocarcinomas in the pylorus was significantly decreased in group 1 compared with the group 2 (NaCl) value (P < 0.05). The incidence of atypical hyperplasias in the fundus was also lower in group 1 than in group 2, although in both cases significantly higher (P < 0.05 and P < 0.01) than in group 4 (no treatment). These results were in good agreement with short-term assay findings whereby lipid peroxidation in the glandular stomach mucosa induced by 4% NaCl ingestion was inhibited by caffeine treatment. In group 3 (caffeine), caffeine intake by itself did not modulate glandular stomach tumour development. The results thus suggest that caffeine inhibits the gastric tumour promotion activity of NaCl in rats.