       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).

