Chemical Carcinogen (3-Methylcholanthrene)-induced Pleomorphic Rhabdomyosarcomas in Fanconi Anemia Fancd2-/-, Fancg-/- (C57BL/6), Fancd2-/- (129/Sv) Mice.

BACKGROUND/AIM: Radiation oncologists are reluctant to treat cancer in Fanconi Anemia (FA) patients due to their lack of homologous recombination repair of DNA strand breaks in normal tissues. To determine the therapeutic effects of irradiation and combination chemotherapy on cancer in syngeneic, radiosensitive FA mice, we derived transplantable cancers of the same genotype in three FA mouse strains.

MATERIALS AND METHODS

Fancd2-/- mice on a C57BL/6 or Sv/129 background and Fancg-/- mice (C57BL/6 background) that received 3-methylcholanthrene (3-MCA), were monitored for the development of subcutaneous tumors.

RESULTS

Tumors were induced at the site of 3-MCA injection, and tumor cell lines were established and found to be transplantable. Explanted tumors were identified as pleomorphic/rhabdomyosarcomas using immunohistochemical biomarkers.

CONCLUSION

These transplantable FA mouse tumor cell lines should be valuable for testing effects of new radiation therapy protocols including FLASH high dose rate radiation delivery, immunotherapies, and combined radiation and chemotherapy treatments for radiosensitive FA patients.