Macrophage-selective toxicity as a mechanism of hydroquinone-induced myelotoxicity
This research has focused upon the role of the bone marrow stroma in the etiology of benzene hematotoxicity. Treatment with the metabolite hydroquinone results in a reduced capacity of the stroma to support myelopoiesis. The goal of this research was to examine stromal cell selective toxicity following hydroquinone treatment. Populations of macrophages and a fibroblastoid cell line (LTF) or primary fibroblasts were developed from mouse bone marrow. Following treatment of with hydroquinone, treated or control fibroblastoid cells were reconstituted with control or treated macrophages, respectively, and the cultures were assayed for their ability to support myelopoiesis. To examine mechanisms of selective toxicity, macrophage and LTF cultures were incubated with 14C-hydroquinone and bioactivation was examined. After 24 hours, macrophages had 16-fold higher levels of bound {sup 14}C than LTF cells. Peroxide-dependent bioactivation in cell homogenates revealed that peroxide could support formation of covalent-binding species in macrophage homogenates but not in LTF homogenates. It was determined that macrophages, but not LTF cells, contained detectable levels of peroxidase activity which was consistent with the postulate that increased binding was due to peroxidase-mediated bioactivation of hydroquinone. Accordingly, purified myeloperoxidase incubated with {sup 14}C-hydroquinone, resulted in bioactivation to a covalent-binding species. This study provided evidence supporting selective bioactivation as a mechanism of selective toxicity of hydroquinone to bone marrow stromal macrophages.
- Research Organization:
- West Virginia Univ., Morgantown, WV (USA)
- OSTI ID:
- 6335916
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
Similar Records
Metabolism of phenol and hydroquinone to reactive products by macrophage peroxidase or purified prostaglandin H synthase
Bioactivation of myelotoxic xenobiotics by human neutrophil myeloperoxidase
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
BENZENE
TOXICITY
BIOASSAY
BONE MARROW
CARBON 14 COMPOUNDS
FIBROBLASTS
HOMOGENATES
MACROPHAGES
METABOLISM
METABOLITES
MICE
QUINONES
TRACER TECHNIQUES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
AROMATICS
BODY
CONNECTIVE TISSUE CELLS
HEMATOPOIETIC SYSTEM
HYDROCARBONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PHAGOCYTES
RODENTS
SOMATIC CELLS
TISSUES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques