N-methyl-N-nitrosourea-induced forestomach neoplastic lesions formed by week 13 following a single intraperitoneal...

CByB6F1-Tg (HRAS)2Jic mice (rasH2 mice) are widely used in 26-week short-term carcinogenicity assessments. To ensure phenotypic stability and carcinogenic sensitivity, a 26-week N-methyl-N-nitrosourea (MNU)-induced carcinogenic susceptibility monitoring study was conducted for quality assurance. The study included (i) comprehensive whole-organ monitoring after colony renewal, and (ii) simplified annual monitoring on production colonies focusing on forestomach tumor formation as the most sensitive endpoint. Retrospective analysis of our 26-week historical data indicated a high incidence of forestomach tumors in mice that were moribund or sacrificed before 13 weeks. Therefore, we compared the 13- and 26-week observation periods to evaluate whether 13 weeks was sufficient for simple carcinogenicity monitoring. RasH2 mice were intraperitoneally administered MNU (75 mg/kg) and observed for 13 and 26 weeks. Both groups exhibited small and large forestomach nodules, including hemorrhagic lesions. The corresponding histopathological features were squamous cell papillomas and carcinomas. The incidence of squamous cell papilloma or carcinoma was 100.0% in both sexes at 13 weeks, which was comparable to that at 26 weeks (100.0% in males and 93.3% in females). These results demonstrated that MNU-induced forestomach tumor can be reliably detected within 13 weeks, indicating that a shortened monitoring period of 13 weeks is sufficient to monitor carcinogenic susceptibility for quality assurance using genotoxic carcinogens in rasH2 mice.