Residual injury to the hemopoietic microenvironment following sequential radiation and busulfan

Journal Article · Sun Aug 01 00:00:00 EDT 1982 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

DOI:https://doi.org/10.1016/0360-3016(82)90581-8· OSTI ID:6374680

Wathen, L M; DeGowin, R L; Gibson, P; Knapp, S A

Earlier studies in mice showed that sequential radiation and cyclophosphamide suppressed marrow stromal cells (MSC) and prevented local hemopoietic repopulation for several months. Because others have shown that busulfan administration caused marrow aplasia, its ability, combined with radiation, to produce a persistent microenvironmental defect in mice was studied. Intraperitoneal administration of four weekly doses of 20 mg/kg busulfan, starting one week after 1500 rad leg irradiation, produced a severe microenvironmental lesion for 6 months reflected by lack of repopulation in femoral marrow to greater than 50% of normal by MSC, hemopoietic stem cells (CFU-S), and granulocyte-macrophage precursors. Differential marrow cell counts revealed that precursors of hemopoietic cells were more profoundly affected than their progeny. Hemopoietic stem cells and MSC failed to recover in busulfan-treated mice at 6 months to the same extent as those treated with cyclophosphamide. In addition, the busulfan-treated mice had an excessive number of myeloid blast cells and a severe erythroid depletion suggesting that these animals were preleukemic. It was concluded that: 1) sequential radiation and busulfan administration caused long-term microenvironmental damage reflected by incomplete repopulation of the femoral marrow and suppression of MSC, and 2) multiple courses of busulfan prevented hemopoietic repopulation longer than a similar regimen of cyclophosphamide.

• Research Organization: Univ. of Iowa Coll. of Medicine, Iowa City
• OSTI ID: 6374680
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 8:8; ISSN IOBPD
• Country of Publication: United States
• Language: English

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560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
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ANIMAL CELLS
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RADIOSENSITIVITY EFFECTS
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