DRUG-INDUCED BONE MARROW INJURY

  • Yunis, Adel A, (PI)

Project: Research project

Description

The objective of this proposal is to eucidate the mechanism by which certain
potential myelotoxins cause bone marrow damage. We will use as the prototype
bone marrow injury induced by chloramphenicol (CAP). Two types of bone marrow
toxicity from CAP will be further investigated: 1. Reversible bone marrow
suppression. Further studies here will include: 1. detailed investigation of
the metabolic effects of CAP on bone marrow mitochondria. b. A study of
CAP-marrow cell interaction using in vitro marrow culture techniques the
mechanism of the protective effect of colony stimulating factor on CFU-C and the
possible protection by other modulators of granulopoiesis from the CAP effect
will be explored. 2. CAP-induced Aplastic Anemia. Two possible pathogenetic
mechanisms will be considered and pursued. a. A biochemical predisposition -
the role of the P-NO2 group of CAP will be explored. The possibililty that bone
marrow aplasia results from irreversible binding of CAP to mitochondrial
ribosomes will be tested. Comparative studies with marrow obtained from
susceptible subjects will be carried out. b. Immune Mechanisms - The possible
role of humoral and cellular immune mechanism in marrow injury from CAP will
also be investigated.
StatusFinished
Effective start/end date9/30/848/31/87

Funding

  • National Institutes of Health

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Chloramphenicol
Bone Marrow
Wounds and Injuries
Pharmaceutical Preparations
Bone and Bones
Colony-Stimulating Factors
Culture Techniques
Aplastic Anemia
Cell Communication
Mitochondria