CHEMOPREVENTIVE ACTIVITY OF OLTIPRAZ AGAINST INDUCTION OF GLANDULAR STOMACH CARCINOGENESIS IN RATS BY N-METHYL-N'-NITRO-N-NITROSOGUANIDINE

The modifying effects of oltipraz on induction of glandular stomach ca rcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were inves tigated in a total of 120 male 6-week-old Wistar rats, divided into si x groups, Groups 1-3 (30 animals each) were given 100 p.p,m, MNNG in t heir drinking water for 10 weeks as an initiation treatment for gastri c cancer induction and respectively fed diets supplemented with 0.04%, 0.02% and 0% oltipraz for 12 weeks, starting 1 week before and finish ing 1 week after the carcinogen exposure, Groups 4-6 (10 animals each) were similarly treated without the application of MNNG. At the end of the 80th experimental week, all surviving animals were autopsied and examined histopathologically for the existence of gastric proliferativ e lesions, The incidence and multiplicity of adenocarcinomas were sign ificantly (P < 0.01) lower in group 1 than in group 3, In addition, th e multiplicity of atypical hyperplasias in the pyloric region was sign ificantly (P < 0.05) decreased in group 1 as compared with the group 3 value, No gastric proliferative lesions were found in groups 4-6, In an additional shortterm experiment, oltipraz significantly reduced cel l proliferative activity (P < 0.01) and elevated glutathione levels (P < 0.05) in the glandular stomach mucosa of rats treated with MNNG, Th us our results clearly indicate that oltipraz can inhibit induction of proliferative glandular stomach lesions by MNNG in the rat.