rasH2™ Mouse Supports Short-Term Skin Carcinogenicity StudiesA recently published article by Mayumi Kawabe et al. has confirmed the effectiveness of rasH2™ mouse in predicting skin carcinogenicity.
The most recent article is a follow-up of an earlier paper published in Veterinary Pathology by Kawabe M, Urano K, et al., which concluded that skin promotion effects could be detected within only eight weeks in the rasH2™ mice, and that the concentration of 4 μg TPA once weekly was sufficient as a positive control.
The most recent paper provided results validating the original paper, concluding that "after initiation with 7,12-dimethylbenz[a]anthracene (DMBA), the promoting potential of 12-O-tetradecanoylphorbol-13-acetate (TPA) on skin tumor development can be detected by an ultra-short-term skin carcinogenicity bioassay using Tg-rasH2 mice and that the detection of skin tumor promotion and carcinogenicity was feasible in only eight weeks."
The conclusion was, "this carcinogenicity bioassay may represent a useful tool for the assessment of the carcinogenicity potential of topically applied chemicals."
Significance for Drug DevelopmentThe short-term skin carcinogenesis bioassay using rasH2™ mice could represent a useful tool for the assessment of drug and chemical safety with cutaneous treatment. The authors explain the potential significance the short-term skin carcinogenesis bioassay using rasH2™ mice could have on the drug development process:
"Since the ICH guidance on testing for carcinogenicity of pharmaceuticals was issued, medium-term carcinogenicity bioassays and 26-week short-term carcinogenicity studies using transgenic mice have been conducted as an alternative to a second traditional long-term (ie, 2-year) carcinogenicity study.
"The ultra-short-term bioassay described in this report may represent a useful screening tool to predict skin carcinogenesis during the early stages of drug development, prior to more laborious and time-consuming regulatory studies."