Chemopreventive Effects of 24 R , 25-Dihydroxyvitamin D 3 , a Vitamin D 3 Derivative , on Glandular Stomach Carcinogenesis Induced in Rats by jV-Methyl-W-nitro-A /-nitrosoguanidine and Sodium Chloride 1

The modifying effects of 24A,25-dihydroxyvitamin D, [24R,25(OH)2D3], a vitamin I), derivative, on glandular stomach carcinogenesis were investigated in male Wistar rats by Af-methyl-JV'-nitro-A'-nitrosoguanidine (MNNG) and sodium chloride exposure during the postinitiation phase. A total of 130 male 6-week-old rats was divided into five groups. Groups 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 supplemented with 10% NaCl for 8 weeks. They were fed a diet containing either 5.0 ppm (group 1) or 2.5 ppm (group 2) 24K,25«>H),1>,or were kept on the basal diet alone (group 3) for the following 57 weeks. Rats in groups 4 and 5 were given 24R,25(OH),I> „¿ as were animals in groups 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 group 3 (70%; P < 0.01). The mean numbers of atypical hyperplasias or adenocarcinomas of the glandular stomachs in groups 1 (0.311 and 2 (0.66) were also significantly decreased (P < 0.01 and P < 0.05, respectively) as compared to the group 3 value (1.21). Thus, the development of cancerous and precancerous lesions in the glandular stomach was de creased by exposure to 24R.25I ( )H Kl>, in a dose-dependent manner. Urinary calcium levels were increased by this vitamin I), derivative (in line with the applied dose) when assayed at 10, 30, and 62 weeks, regardless of the MNNG + NaCl treatment The present results clearly indicate that 24K.25(OH),I), exerts Chemopreventive effects, possibly by influencing cal cium pharmacodynamics, when given during the postinitiation phase of glandular stomach carcinogenesis in rats.