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X-ray induction of tumors were examined in five-week-old male CD(SD) : Crj rats, treated with two 10 Gy doses to the gastric region with a 3-day interval (total 20 Gy). After irradiation, the rats received a 1% NaCI supplement in the diet and survivors were killed 22 months after the first X-irradiation. The total tumor incidence was 59% (48 of 82 effected rats), the first animal demonstrating a sarcoma at day 273. Islet tumors of the pancreas appeared from the 455 day time point. Pancreatic and kidney tumors developed in 15 rats (18%) each, and apocrine tumors at the irradiated site and sarcomas in 9 rats (11%) and 5 (6%), respectively. Gastric tumors were found in 3 rats (4%). Immunohistochemistry revealed the islet tumor cells to be generally positive for insulin, although some cells contained somatostatin or glucagon, but not gastrin. The present results thus showed that the insulinomas and tumors other than gastric lesions are induced by X-irradiation of the upper peritoneal region.

The stomach region of male hypocatalasemic (Cbs), C3H, and BALB mice of both sexes was irradiated once with a dose of 20 Gy of X-ray. After irradiation the Cbs mice were administered with 0.1% hydrogen peroxide (H2O2) solution as their drinking water, or 10% sodium chloride (NaCl) in their diet. The resultant total tumor incidences were 50% to 100% by the end of the experiment after 13 months. More female mice died in the early phase after X-irradiation than males. Well differentiated tumors were observed in the glandular stomachs of 35 to 100% and signet ring cell carcinomas in 0 to 22% of the animals. Squamous cell carcinomas (SCCs) were most frequently encountered in BALB mice of both sexes. The present results indicate that X-ray induction of adenocarcinomas, signet ring cell carcinomas, and SCCs of the glandular stomach in CS mice is not promoted by H2O2 or NaCl.

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