CHEMOPREVENTIVE EFFECTS OF 24R,25-DIHYDROXYVITAMIN-D-3, A VITAMIN-D-3DERIVATIVE, ON GLANDULAR STOMACH CARCINOGENESIS INDUCED IN RATS BY N-METHYL-N'-NITRO-N-NITROSOGUANIDINE AND SODIUM-CHLORIDE

The modifying effects of 24R,25-dihydroxyvitamin D-3 [24R,25(OH)(2)D-3 ], a vitamin 4 derivative, on glandular stomach carcinogenesis were in vestigated in male Wistar rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium chloride exposure during the postinitiation phase. A total of 130 male 6-week-old rats was divided into five groups. Grou ps 1-3 (consisting of 30 rats/group) were given MNNG in drinking water at a concentration of 100 ppm and were simultaneously fed a diet supp lemented with 10% NaCl for 8 weeks. They were fed a diet containing ei ther 5.0 ppm (group 1) or 2.5 ppm (group 2) 24R,25(OH)(2)D-3 or were k ept on the basal diet alone (group 3) for the following 57 weeks. Rats in groups 4 and 5 were given 24R,25(OH)(2)D-3, as were animals in gro ups 1 and 3, but did not receive the MNNG + NaCl treatment. The total incidence of combined atypical hyperplasias and adenocarcinomas in the glandular stomachs was significantly lower in group 1 (24%) than in g roup 3 (70%; P < 0.01). The mean numbers of atypical hyperplasias or a denocarcinomas of the glandular stomachs in groups 1 (0.31) and 2 (0.6 6)were also significantly decreased (P < 0.01 and P < 0.05, respective ly) as compared to the group 3 value (1.21), Thus, the development of cancerous and precancerous lesions in the glandular stomach was decrea sed by exposure to 24R,25(OH)(2)D-3 in a dose-dependent manner, Urinar y calcium levels were increased by this vitamin D-3 derivative (in lin e with the applied dose) when assayed at 10, 30, and 62 weeks, regardl ess of the MNNG + NaCl treatment. The present results clearly indicate that 24R,25(OH)(2)D-3 exerts chemopreventive effects, possibly by inf luencing calcium pharmacodynamics, when given during the postinitiatio n phase of glandular stomach carcinogenesis in rats.