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Induction of sarcomas in athymic mice
Summary
Serial passage of human xenografts in athymic mice induced murine sarcomas. These aggressive tumors, identified by lactate dehydrogenase isozyme and histology, contained murine leukemia virus but lacked detectable murine sarcoma virus.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Serial passage of human xenografts in athymic mice is a common technique for studying human tumor growth.
- Murine stromal tissue can undergo changes during prolonged xenograft passages.
Purpose of the Study:
- To investigate the spontaneous induction of sarcomas in murine stromal tissue associated with human xenografts.
- To characterize the biological and virological properties of induced murine sarcomas.
Main Methods:
- Serial passage of 50 human xenografts in athymic mice over 5 years.
- Monitoring tumor changes using lactate dehydrogenase isozyme profiling and histology.
- Establishment of induced sarcomas in tissue culture and characterization of cell lines.
- Assay for reverse transcriptase activity and electron microscopy for virus detection.
Main Results:
- Two instances of murine sarcoma induction in stromal tissue were observed, with sarcomas outgrowing human xenografts.
- Sarcoma cell lines exhibited malignant morphological and growth characteristics and were tumorigenic.
- High levels of murine leukemia virus reverse transcriptase activity were detected; type C virus particles observed.
- Murine sarcoma virus was not detected by in vitro transformation or in vivo sarcoma formation assays.
Conclusions:
- Human xenograft passage in athymic mice can lead to the spontaneous induction of malignant murine sarcomas.
- These sarcomas are associated with murine leukemia virus but not necessarily murine sarcoma virus.
- Further investigation into the high plasma membrane ATP phosphohydrolase levels in these sarcomas is warranted.