Document 0786
 DOCN  M94B0786
 TI    Protective effects of swainsonine against toxicity of chemotherapeutic
       drugs (Meeting abstract).
 DT    9412
 AU    Klein JL; George MD; Roberts JD; Kurtzberg J; Breton P; Chermann JC;
       Olden K; Lab of Molecular Carcinogenesis, NIEHS, Research Triangle
       Park,; NC 27709
 SO    Proc Annu Meet Am Assoc Cancer Res; 35:A1909 1994. Unique Identifier :
       AIDSLINE ICDB/94603595
 AB    Swainsonine, a plant-derived alkaloid, abrogates the cytotoxicity of
       drugs commonly used in cancer and AIDS therapy. In a murine bone marrow
       progenitor colony-forming assay, as previously published, CFU-E were
       more sensitive to AZT toxicity than were CFU-GM. Addition of swainsonine
       to the medium containing AZT increased 5-fold the number of CFU-E and
       CFU-GM. Similar experiments were carried out with human bone marrow. In
       a preliminary study, addition of 20 uM AZT to the medium decreased the
       number of CFU-GM colonies to 18% compared to untreated cells; the
       presence of 10 ug/ml of swainsonine restored the number of CFU-GM to 63%
       of the control. In a more extensive set of studies in a second
       laboratory, we used marrow from four different donors and consistently
       obtained an antagonistic effect of swainsonine against the AZT toxicity
       on CFU-GM progenitors. The protective effect of swainsonine was also
       observed in vivo when animals were treated with anticancer drugs such as
       cyclophosphamide (CPM). Swainsonine treatment (10 ug/injection, 2
       injections per day) led to an almost complete protection of mice (90%
       survival) treated with high doses (10 mg) of CPM (50% survival with CPM
       alone). The same protective effect was observed when animals were
       treated with other drugs, such as methotrexate and doxorubicin.
 DE    Animal  Antineoplastic Agents/ANTAGONISTS & INHIB/*TOXICITY  Cells,
       Cultured  Colony-Forming Units Assay  Cyclophosphamide/*TOXICITY
       Hematopoietic Stem Cells/CYTOLOGY/*DRUG EFFECTS  Human  Mice
       Swainsonine/*PHARMACOLOGY  Zidovudine/*TOXICITY  MEETING ABSTRACT

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