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M94B0786.TXT
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1994-11-11
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).