GASTRIC CARCINOGENESIS IN RATS GIVEN HYPERTONIC SALT AT DIFFERENT TIMES BEFORE A SINGLE-DOSE OF N-METHYL-N'-NITRO-N-NITROSOGUANIDINE

A 1-ml dose of 4.5 M NaCl was given intragastrically to male Wistar ra ts at 10 min, 1 h, 4 h, 12 h, 24 h or 48 h before a single intragastri c dose of 250 mg/kg N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After 52 weeks the incidence of forestomach squamous cell carcinoma was 21 % in control animals receiving MNNG alone. The cancer incidence in the forestomach varied with the time elapsed between application of NaCl MNNG, and was significantly increased in animals pretreated with NaCl 4 h (43%),12 h (54%) and 24 h (41%) before MNNG. These results show th at salt has a cocarcinogenic effect on initiation of forestomach carci nogenesis in rats, and that this effect depends on the time interval b etween pretreatment with NaCl and application of MNNG. Gastric adenoca rcinomas occurred more frequently in the antrum (78%) than in the corp us (22%). The incidence of gastric adenocarcinoma in animals pretreate d with salt before application of MNNG (11%-22%) was not significantly influenced by the time elapsed between pretreatment with salt and app lication of MNNG, and did not differ from animals receiving MNNG alone (18%). The lack of a cocarcinogenic effect of NaCl on glandular gastr ic carcinogenesis might be due to the use of dimethyl/sulfoxide as sol vent for MNNG.