Late tissue-specific toxicity of total body irradiation and busulfan in a murine bone marrow transplant model Journal Article


Authors: Down, J. D.; Berman, A. J.; Warhol, M.; van Dijken, P. J.; Ferrara, J. L. M.; Yeap, B.; Hellman, S.; Mauch, P. M.
Article Title: Late tissue-specific toxicity of total body irradiation and busulfan in a murine bone marrow transplant model
Abstract: Total body irradiation (TBI) and busulfan were compared for late effects in a murine model of bone marrow transplantation (BMT). Male C57BL/6 mice were given fractionated TBI or busulfan given in 4 equal daily doses followed by infusion of 107 syngeneic bone marrow cells. Total doses of 16.4 Gy TBI and 3.4 mg busulfan were chosen for their equivalence in inducing near complete engraftment of allogeneic marrow from donor mice of the LP strain. The two treatment groups had a late wave of mortality starting at about 80 weeks after transplantation. Specific tissue damage was manifested in bone marrow stem cells, splenic T-cell precursors, hair greying and cataract formation for both TBI and busulfan but to varying degrees. Severe nephrotoxicity and anemia were observed only after TBI. Although both busulfan and TBI kill early marrow stem cells and are effective preparative agents in bone marrow transplantation, their effects on other stem cell and organ systems are not similar. In addition, many of the injuries seen are late to occur. The delayed expression of injury deserves careful long-term evaluation of BMT recipients before the therapeutic potential of effective preparative regimens can be fully appreciated. © 1989.
Keywords: busulfan; mortality; nonhuman; t-lymphocytes; mouse; animal; mice; nephrotoxicity; bone marrow; hemolysis; radiotherapy; animal model; weight loss; mice, inbred c57bl; histology; late effects; hair color; whole body radiation; kidney; lung; cataract; hematopoiesis; drug therapy; bone marrow transplantation; nephropathy; whole-body irradiation; total body irradiation; intraperitoneal drug administration; male; priority journal; support, u.s. gov't, p.h.s.
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 17
Issue: 1
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 1989-07-01
Start Page: 109
End Page: 116
Language: English
DOI: 10.1016/0360-3016(89)90377-5
PUBMED: 2663795
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 14 April 2020 -- Source: Scopus
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  1. Samuel Hellman
    25 Hellman