Interlaboratory comparison of the CB6F1-Tg rasH2 rapid carcinogenicity testing model

Area of Science:

• Toxicology
• Genetically Engineered Models
• Carcinogenesis

Background:

• Genetically engineered mouse models are crucial for cancer hazard identification.
• The CB6F1-Tg rasH2 transgenic mouse is a model under evaluation for carcinogenicity bioassays.

Purpose of the Study:

• To conduct an interlaboratory comparison of the CB6F1-Tg rasH2 transgenic mouse model's performance in cancer bioassays.
• To assess the reliability of this model in identifying chemical carcinogens and non-carcinogens across different research sites.

Main Methods:

• An interlaboratory comparison study was performed concurrently in the United States and Japan.
• Known human and rodent carcinogens (p-cresidine, vinyl carbamate, cyclosporin A) and non-carcinogens (p-anisidine, resorcinol) were tested at carcinogenic or high doses.
• Melphalan was excluded due to administration vehicle complications.

Main Results:

• The CB6F1-Tg rasH2 transgenic mouse model demonstrated good concordance in outcomes between the two laboratories for five tested chemicals.
• Vinyl carbamate induced lung adenomas/carcinomas and splenic hemangiosarcomas, showing a strong positive response.
• p-Cresidine was positive for urinary bladder transitional neoplasia; cyclosporin A, p-anisidine, and resorcinol were negative.

Conclusions:

• The CB6F1-Tg rasH2 transgenic mouse model shows promise for reliable cancer hazard identification, particularly for potent carcinogens and non-carcinogens.
• Further modifications to study design, such as increasing animal numbers and study duration, may be necessary for detecting weaker carcinogenic potentials.