抄録
This study was performed to validate the performance of alternative carcinogenicity bioassays using commonly-accepted transgenic mouse models given known carcinogens in our laboratory. Positive control materials produced expected tumors in both the p53+/- and Tg.rasH2 mouse. Therefore, use of these models for bioassays has been validated in this laboratory. p53+/- mice, 25/sex/group, received vehicle (corn oil) or 400 mg/kg/day of p-cresidine by oral intubation (gavage) for 6 months. Tg.rasH2 mice, 25/sex/group, received vehicle (saline) or 75 mg/kg N-methyl-N-nitrosourea (MNU) as a single intraperitoneal dose, followed by a 6-month holding period. Clinical signs and body weights were monitored. Moribund animals and all animals surviving after 6 months were euthanized and necropsied.
p53+/- mice had good survival but reduced body weight gains (60–70% lower than control). Neoplasms associated with p-cresidine administration occurred primarily in the urinary bladder (squamous cell carcinoma in 5/50 animals, transitional cell carcinoma in 31/50 and leiomyosarcoma in one animal). These are expected effects and are consistent with published studies.
Tg.rasH2 mice had poor survival (34%) but normal body weight gains. Neoplasms associated with MNU administration included squamous cell papilloma (multiple locations) in 24/50 animals, squamous cell carcinoma (forestomach) in 8/50 and malignant lymphoma in 30/50. These are expected effects and are consistent with published studies.
