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Hypocatalasemic mice were treated with N-methyl-N-nitrosourea (MNU) in their drinking water or gastric intubation for 16 weeks or were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in their drinking water for 6 months. With MNU treatment in the drinking water, well differentiated tumors were observed in the glandular stomachs of one male (4%) and 5 female (15%) animals. Sarcomas of the dermis also appeared in 10 males (40%). Adrenal lesions developed in I I females (35%) along with kidney, ovary, and uterus tumors. In the Group given MNU intubation, squamous cell carcinomas of the forestomach appeared from 122 days after the first treatment, reaching incidences of 81% in males, 94% in females, with invasion of the diaphragm in 3 male cases and the diaphragm, liver, pancreas, or adrenal in I I female cases. Glandular stomach tumors occurred in 12 males (52%), with 3 being signet ring cell carcinomas, and in 12 females (35%). In a sub-Group undergoing forestomach removal after MNU intubation esophagectasis appeared from 80 days after the operation at incidences of 63% in males and 74% in females. The glandular stomach tumors including 3 signet ring cell carcinomas were found in 17 of 46 (40%) males, 2 of 18 (11%) females demonstrated lesion, one being a signet ring cell carcinoma. In the Group receiving MNNG treatment, anemia appeared from the 5.5 month time point and no gastric tumors were observed. The present results do not support the conclusion that MNU induction of glandular stomach lesions in hypocatalasemic mice may provide a useful model of signet ring cell carcinomas

Gardenia yellow (GY) is a widely used natural yellow colorant for foods and clothing. In this study, we have examined the sub-chronic and chronic effects of GY in mice. Both sexes of C57BL/ HeN mice of six weeks old were used. GY was dissolved in distilled water and orally administered. In the sub-chronic study, 0, 0.05, 0.1, 0.2, 0.4, 0.8, and 1.6% of GY were given to mice and they were observed for 12 weeks. During this period, there were no abnormal changes detected in survivals, body weight increases or pathology of organs. It was concluded that GY had no toxicity up to 1.6% in drinking water. The concentrations of 0, 0.2 and 0.8% of GY were chosen for the further carcinogenicity study by observing for 95 weeks. In this chronic toxicity study, there was a 4.5 to 15.4% development of plasmacytoma in the mesenteric lymph nodes that has been known to occur spontaneously in C57BL mice. The pituitary and liver tumors were also noted regardless of the GY doses. The unique observation in this experimental series is the development of hepatosis that is characterized with enlarge-ments of liver, spleen, kidney, and lymph nodes, although they were not related to the doses of GY. These findings were rather systemic and this syndrome may be categorized as amyloidosis. The present study did not show any carcinogenicity or other chronic disorders by GY.