THE EFFECT OF UBENIMEX† ON N-METHYL-N'-NITRO-N-NITROSOGUANIDINE-INDUCED STOMACH TUMOR IN RATS

The effect of ubenimex on the progression of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced stomach tumor in rats was studied. Tumor induction was performed by giving MNNG via drinking water for 34 weeks. Ubenimex was ip administered twice a week at 0.5mg/kg for 84 weeks in one group and 49 weeks in another starting from the first and 36th weeks after initiation of MNNG administration, respectively. The stomachs were endoscopically examined 2 times. At the 64th week after initiation of MNNG administration tumorous lesions were observed with about 70% of the rats in both ubenimex administration groups. In the ubenimex non-administration group nearly 90% of the rats had the lesions. After completion of ubenimex administration almost all the rats had the lesions in the three groups but the sizes were much smaller with the two ubenimex administration groups. Almost all of these lesions were histopathologically identified as tumorous. The tumor volume per rat in the two ubenimex administration groups from the 1 and 36th weeks was 21.0 and 19.2% of the volume in the control group, respectively. Tumor number per rat was similar among the three groups. The natural killer activity of rats was also examined after completion of the above experiment. The activity markedly increased when ubenimex was administered from the 36th week after initiation of MNNG administration. When ubenimex was administered from the first week, the activity did not increase demonstratively. From all the results described above we conclude that ubenimex exerts an inhibitory action against the progression of MNNG-induced stomach tumor in rats. Contribution of the increase of natural killer activity to ubenimex antitumor action may be dependent on schedule of ubenimex administration.