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

In Vivo. 2024 Nov-Dec;38(6):2582-2590. doi: 10.21873/invivo.13734.

Abstract

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.

Keywords: 3-methylcholanthrene; Fanconi anemia mouse models; chemical carcinogen.

MeSH terms

  • Animals
  • Carcinogens / toxicity
  • Cell Line, Tumor
  • Disease Models, Animal
  • Fanconi Anemia Complementation Group D2 Protein* / genetics
  • Fanconi Anemia Complementation Group G Protein* / genetics
  • Fanconi Anemia* / genetics
  • Humans
  • Methylcholanthrene*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout*
  • Rhabdomyosarcoma* / etiology
  • Rhabdomyosarcoma* / genetics
  • Rhabdomyosarcoma* / pathology

Substances

  • Carcinogens
  • Fancd2 protein, mouse
  • Fanconi Anemia Complementation Group D2 Protein
  • Fanconi Anemia Complementation Group G Protein
  • Methylcholanthrene