Inhibition of gastric tumorigenesis by alpha-difluoromethylornithine in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine.

Male Wistar rats were treated concurrently with a combination of the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; CAS 70-25-7) and the polyamine-synthesis inhibitor alpha-difluoromethylornithine (DFMO) at two different doses of 0.5% and 1.0% (w/v). Experimental groups were treated with (I) MNNG alone (n = 25), (II) MNNG plus 0.5% (w/v) DFMO (n = 25), (III) MNNG plus 1.0% (w/v) DFMO (n = 25), (IV) 1.0% (w/v) DFMO alone (n = 25). Group V represented untreated controls (n = 20). Both the carcinogen and DFMO were administered in drinking water. The treatment time with the carcinogen and DFMO was 35 weeks. After treatment was completed animals were followed for an additional 50 weeks to cover a total observation time of 85 weeks. Significantly fewer animals developed gastric adenocarcinoma in the two groups of animals that received a combined treatment of MNNG plus DFMO compared to animals treated with the carcinogen alone (P < 0.05 and 0.005). No benign or malignant neoplastic lesions were observed in the stomach or duodenum of animals treated with DFMO alone or in untreated controls. It is concluded that concurrent treatment with DFMO prevents the development of malignant gastric epithelial tumors induced by MNNG in rats.