N-METHYL-N'-NITRO-N-NITROSOGUANIDINE-INDUCED CARCINOGENESIS - DIFFERENTIAL PATTERN OF UPPER GASTROINTESTINAL-TRACT TUMORS IN WISTAR RATS AFTER SINGLE OR CHRONIC ORAL DOSES

Male Wistar rats were treated with N-methyl-N'-nitro-N-nitrosoguanidin e (MNNG) either as a single dose of 50, 125 or 250 mg/kg given by gava ge or via drinking water for 28 weeks at a concentration of 40, 80 or 160 /mug/ml, in the case of the higher concentration reverting to 80 m ug/ml after the first 8 weeks. The single dose regimen had no effect o n water intake or body weight, but the chronic exposure led to a dose- dependent reduction in water intake that was paralleled by a slower we ight gain, with the final body weights at approximately 90, 84 and 79% of the control weight values. The combined yield of benign and malign ant tumours (79-100% of the animals treated) occurred in the forestoma ch in the case of the single doses, whereas the chronic exposure resul ted in a maximum yield of tumours located in the pyloric region of the glandular stomach (64-100% of animals treated). The principal histolo gical types of tumours induced were squamous cell papilloma and carcin oma in the forestomach and adenocarcinoma in the pylorus. There was a persistent, but low yield (25-30% of animals treated) of tumours in th e jejunum, mainly adenocarcinoma, after administration via drinking wa ter, whereas after single doses, multiple solitary cysts and cholangio ma (30% and 25-70% respectively of the animals treated) were found in the liver. This report differs from earlier reports in that marked eff ects were noted on water consumption and body weight gain and that tum our induction can be achieved after much shorter periods of exposure t han previously reported in the literature. These data confirm the tiss ue specificity of MNNG when given either as a single or chronic dose r egimen and provide a suitable model for the investigation of the targe t cell specificity of tumour induction.