Comparison of 37.5 mg/kg and 75 mg/kg dose of N-methyl-N-nitrosourea in Tg.rasH2 mice as positive control in 26-week carcinogenicity assays

ACT 2023 -- CByB6F1-Tg(HRAS)2Jic (Tg.rasH2) mouse model is the currently accepted transgenic mouse model for evaluation of carcinogenic potential of prospective new therapeutics. The model is run in place of a 2-year mouse carcinogenicity assay and can be completed in 26-weeks. Although the model has been in use for many years, each study still requires a positive control group to assure that the model responds to a carcinogen as intended. N-methyl-N-nitrosourea (MNU) is a commonly used positive control agent to induce tumors in this mouse model and is administered as a single dose in many U.S.-based sites as 75 mg/kg intraperitoneally while in the UK has been administered successfully at 37.5 mg/kg intraperitoneally. The aim of this evaluation was to compare the Labcorp Early Development data from the U.S. to the UK to evaluate whether 37.5 mg/kg is sufficient to evaluate carcinogenic potential in the Tg.rasH2 and evaluate survivability with each dose level.