Protective effects of swainsonine against toxicity of chemotherapeutic drugs (Meeting abstract).

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Protective effects of swainsonine against toxicity of chemotherapeutic drugs (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 35:A1909 1994. Unique Identifier : AIDSLINE ICDB/94603595
Klein JL; George MD; Roberts JD; Kurtzberg J; Breton P; Chermann JC; Olden K; Lab of Molecular Carcinogenesis, NIEHS, Research Triangle Park,; NC 27709

Abstract: 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.

Keywords: 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 ABSTRACT
941230
M94C4323

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