Induction of TGF-β by Irradiation or Chemotherapy in Fanconi Anemia (FA) Mouse Bone Marrow Ιs Modulated by Small Molecule Radiation Mitigators JP4-039 and MMS350

Autor: Shaonan Cao, Darcy Franicola, Donna Shields, B. Rhieu, Peter Wipf, Michael W. Epperly, Tracy Dixon, Hong Wang, Xichen Zhang, Joel S. Greenberger
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
Mice
129 Strain
medicine.medical_treatment
Blotting
Western
Radiation-Protective Agents
General Biochemistry
Genetics and Molecular Biology
Cell Line
Tissue Culture Techniques
03 medical and health sciences
0302 clinical medicine
Drug Therapy
Bone Marrow
Ethers
Cyclic
Transforming Growth Factor beta
Fanconi anemia
In vivo
medicine
Animals
Busulfan
Melphalan
Cells
Cultured
Mice
Knockout
Pharmacology
Chemotherapy
biology
business.industry
Transforming growth factor beta
Myeloablative Agonists
Total body irradiation
medicine.disease
Mice
Inbred C57BL
Fanconi Anemia
030104 developmental biology
Cytokine
medicine.anatomical_structure
Sulfoxides
030220 oncology & carcinogenesis
Immunology
Cancer research
biology.protein
Nitrogen Oxides
Bone marrow
business
Vidarabine
Whole-Body Irradiation
Research Article
medicine.drug
Zdroj: In Vivo. 31:159-168
ISSN: 1791-7549
DOI: 10.21873/invivo.11040
Popis: Background/aim Total-body irradiation and/or administration of chemotherapy drugs in bone marrow transplantation induce cytokines that can suppress engraftment. Fanconi Anemia (FA) patients have a hyperactive responsiveness to the inhibitory cytokine, transforming growth factor-beta (TGF-β). Small molecule radiation mitigator drugs, JP4-039 and MMS350, were evaluated for suppression of irradiation or drug-induced TGF-β. Materials and methods In vivo induction of TGF-β by total-body ionizing irradiation (TBI), L-phenylalanine mustard (L-PAM), busulfan or fludarabine, was quantified. In parallel, mitigator drug amelioration of TGF-β induction in FA D2-/- (FANCD2-/-) mouse bone marrow, was studied in vitro. Tissue culture medium, cell lysates, and mouse plasma were analyzed for TGF-β levels. Results Induction of TGF-β levels in FANCD2-/- and FANCD2+/+ mice and in mouse bone marrow were modulated by both JP4-039 and MMS350. Conclusion Bone marrow transplantation in FA recipients may benefit from administration of small molecule agents that suppress TGF-β induction.
Databáze: OpenAIRE
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