Historical control data of spontaneous tumors in transgenic CByB6F1-Tg(HRAS)2Jic (Tg.rasH2) mice
Madhav G Paranjpe1, Reem H Elbekaei, Sudhir A Shah
1BioReliance Corporation, 14920 Broschart Road Rockville, MD 20850, USA.
Abstract:
The Tg.rasH2 mouse is a hemizygous transgenic mouse, approved by regulatory agencies for carcinogenicity assessment. However, the absence of a historical database for the incidence of spontaneous neoplasms has subsequently led to reluctance by some pharmaceutical companies to adopt the use of this short-term carcinogenicity assay. Our laboratory has generated a database summarizing the mortality, body weights, and the incidence of spontaneous tumors in 1420 male and female mice assigned to 26 studies conducted at our facility. In addition, we present the incidence of tumors in positive control mice treated with urethane from these studies. Mortality in the vehicle-treated Tg.rasH2 mouse was low (average of 1% in each study). The most common spontaneous tumors in the Tg.rasH2 mice were alveolar bronchiolar adenoma of the lungs (10.14% in males and 5.77% in females) and hemangiosarcoma of the spleen (3.66% in both males and females). The incidence of all other tumors was generally very low. In the positive control, urethane-treated animals, the incidence of alveolar bronchiolar adenomas and alveolar bronchiolar carcinomas in the lungs was 93.69% and 42.88% in males and 92.43% and 72.79% in females, respectively. In addition, the incidence of splenic hemangiosarcomas in urethane-treated males was 89.18% and 92.25% in females. The 6-month Tg.rasH2 assay is more precise, faster, and more economical than the conventional 2-year mouse assays because of the low incidence of background tumors, very high survival, shorter duration, and the lower number of animals used.
Insights
The Tg.rasH2 mouse assay provides a reliable short-term carcinogenicity assessment. This study establishes a historical database for spontaneous tumor incidence, supporting its use in drug development.
Area of Science:
- Toxicology and Carcinogenesis
- Transgenic Animal Models
- Regulatory Science
Background:
- The Tg.rasH2 mouse is an approved model for carcinogenicity assessment.
- Lack of historical spontaneous neoplasm data has limited its adoption.
- Pharmaceutical companies require robust historical data for assay validation.
Purpose of the Study:
- To generate a comprehensive historical database for spontaneous tumor incidence in Tg.rasH2 mice.
- To present tumor incidence data in positive control (urethane-treated) mice.
- To support the validation and wider adoption of the Tg.rasH2 assay.
Main Methods:
- Compiled data from 1420 male and female Tg.rasH2 mice across 26 studies.
- Recorded mortality, body weights, and spontaneous tumor incidence.
- Included urethane-treated positive controls to establish assay sensitivity.
Main Results:
- Low mortality (1%) in vehicle-treated Tg.rasH2 mice.
- Most common spontaneous tumors: lung alveolar adenoma (5.77-10.14%) and spleen hemangiosarcoma (3.66%).
- High tumor incidence in urethane-treated controls (e.g., lung tumors >90%, spleen hemangiosarcoma >89%).
Conclusions:
- The Tg.rasH2 mouse assay demonstrates high survival and low background tumor rates.
- The established database supports the Tg.rasH2 assay's precision, speed, and economy.
- This short-term assay is a viable alternative to conventional 2-year carcinogenicity studies.
