rasH2 Supports Short-Term Skin Carcinogenicity StudiesA recently published article by Mayumi Kawabe et al. has confirmed the effectiveness of rasH2 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."