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Transponder-induced sarcoma in the heterozygous p53+/- mouse
K T Blanchard1, C Barthel, J E French
1Department of Toxicology and Safety Assessment, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877, USA. kblancha@rdg.boehringer-ingelheim.com
Toxicologic Pathology
|October 21, 1999
Summary
Radio transponder implants in p53+/- mice unexpectedly caused malignant sarcomas. These tumors arose from mesenchymal dysplasia, independent of drug treatments, highlighting a potential confounder in carcinogenicity studies.
Area of Science:
- Oncology
- Toxicology
- Animal Models
Background:
- p53+/- transgenic mice are evaluated as a rapid alternative to traditional 2-year rodent carcinogenicity bioassays.
- Subcutaneous implantation of radio transponder identification devices is a common procedure in rodent studies.
Purpose of the Study:
- To assess the carcinogenicity of oxymetholone in p53+/- mice using p-cresidine as a positive control.
- To evaluate the safety and potential side effects of radio transponder implantation in this model.
Main Methods:
- Male and female p53+/- mice were implanted with radio transponders during a 26-week study.
- Tumor development and characteristics were monitored clinically and microscopically.
- Animals received oxymetholone or p-cresidine, with control groups included.
Main Results:
- 18 out of 177 mice developed subcutaneous malignant sarcomas at transponder implant sites.
- Tumors were undifferentiated sarcomas, not linked to oxymetholone or p-cresidine treatment.
- A preneoplastic change, "mesenchymal dysplasia," was observed originating from the transponder's anchoring barb, preceding sarcoma development.
Conclusions:
- Radio transponders can induce sarcoma development in p53+/- mice, independent of chemical exposure.
- Mesenchymal dysplasia is identified as a preneoplastic response to the transponder.
- The findings suggest transponder implantation is a significant confounder for carcinogenicity studies in this model.