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- Document 0305
- DOCN M9620305
- TI Influence of human granulocyte-macrophage colony stimulating
- factor/interleukin-3 fusion protein (PIXY321) on the hematopoietic
- toxicity associated with anti-viral drugs (zidovudine and didanosine) in
- vitro using normal human marrow cells.
- DT 9602
- AU Gallicchio VS; Hughes NK; Division of Hematology/Oncology, Markey Cancer
- Center, University; of Kentucky, Lexington 40536-0084, USA.
- SO Life Sci. 1995 Sep 22;57(18):PL265-73. Unique Identifier : AIDSLINE
- MED/96035980
- AB The antiviral drugs didanosine (ddI) and zidovudine (AZT), synthetic
- nucleoside analogs, have been used in the treatment of acquired
- immunodeficiency syndrome (AIDS). Although clinical use of zidovudine
- (AZT) is still widely used, it is associated with the development of
- virus disease resistance and toxicity to the hematopoietic system.
- Alternative nucleoside reverse transcriptase derivatives such as
- didanosine (ddI) have been developed in order to reduce the incidence of
- virus disease resistance and hematological toxicity. We report here
- studies designed to ev evaluate the toxicity profile comparing
- didanosine (ddI) with zidovudine (AZT) when used alone or in combination
- with normal non-adherent, T-cell depleted human marrow cells plated in
- the presence or absence of the human cytokine fusion protein of
- granulocyte-macrophage colony stimulating factor and interleukin-3
- (PIXY321). As expected, didanosine (ddI) was less toxic for human
- hematopoietic progenitor cells, i.e., CFU-GEMM, CFU-GM, CFU-Meg, and
- BFU-E than zidovudine. Toxicity was additive when didanosine (ddI) and
- zidovudine (AZT) were combined. In the absence of drugs PIXY321 colony
- formation was increased for all progenitor cells cultured. In the
- presence of didanosine (ddI) or zidovudine (AZT), either as
- single-agents or combined, PIXY321 reduced toxicity significantly. These
- results demonstrate PIXY321 is an effective cytokine capable of
- reversing the toxicity associated with anti-viral drugs when used in
- vitro where didanosine (ddI) is less toxic than zidovudine (AZT);
- however their suppression of hematopoietic progenitors is additive when
- combined.
- DE Antiviral Agents/PHARMACOLOGY Bone Marrow/*DRUG EFFECTS Cells,
- Cultured Didanosine/*PHARMACOLOGY/*TOXICITY Dose-Response
- Relationship, Drug Granulocyte-Macrophage Colony-Stimulating
- Factor/*PHARMACOLOGY Growth Substances Hematopoietic Stem Cells/*DRUG
- EFFECTS Human In Vitro Interleukin-3/*PHARMACOLOGY Recombinant
- Fusion Proteins/*PHARMACOLOGY Support, U.S. Gov't, Non-P.H.S. Support,
- U.S. Gov't, P.H.S. Zidovudine/*PHARMACOLOGY/*TOXICITY JOURNAL ARTICLE
-
- SOURCE: National Library of Medicine. NOTICE: This material may be
- protected by Copyright Law (Title 17, U.S.Code).
-
-