Transponder-induced sarcoma in the heterozygous p53(+/-) mouse

Heterozygous p53(+/-) transgenic mice are being studied for utility as a sh ort-term alternative model to the 2-yr rodent carcinogenicity bioassay. Dur ing a 26-wk study to assess the potential carcinogenicity of oxymetholone u sing p-cresidine as a positive control, glass/polypropylene microchips (rad io transponder identification devices) were subcutaneously implanted into m ale and female p53(+/-) mice. During week 15, the first palpable mass was c linically observed at an implant site. This rapidly growing mass virtually quadrupled in size by week 25. Microscopic examination of all implant sites revealed that 18 of 177 animals had a subcutaneous histologically malignan t sarcoma. The neoplasms were characterized as undifferentiated sarcomas un related to drug treatment, as indicated by the relatively even distribution among dose groups, including controls. An unusual preneoplastic mesenchyma l change characterized by the term "mesenchymal dysplasia" was present in m ost groups and was considered to be a prodromal change to sarcoma developme nt. The tumors were observed to arise from dysplastic mesenchymal tissue th at developed within the tissue capsule surrounding the transponder. The pre neoplastic changes, including mesenchymal dysplasia, appeared to arise at t he transponder's plastic anchoring barb and then progressed as a neoplasm t o eventually surround the entire microchip. Capsule membrane endothelializa tion, inflammation, mesenchymal basophilia and dysplasia, and sarcoma were considered unequivocal preneoplastic/neoplastic responses to the transponde r and were not related to treatment with either oxymetholone or p-cresidine .