|
|
 Previous Article | Table of Contents | Next Article 
Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition
of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by
hydroquinone and prevention of benzene-induced hematotoxicity in mice by
IL-1 alpha
JF Renz and GF Kalf
Department of Biochemistry and Molecular Biology, Jefferson Medical
College, Thomas Jefferson University, Philadelphia, PA.
Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic
anemia and acute leukemia. The stromal macrophage that produces
interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target
of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have
been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ),
a toxic bone marrow (BM) metabolite of BZ, causes time- and
concentration-dependent inhibition of processing of the 34-Kd
pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine
P388D1 macrophages and BM stromal macrophages, as measured by Western
immunoblots of cell lysate proteins using a polyclonal rabbit antimurine
IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on
the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha
precursor or on cell viability or DNA and protein synthesis. Stromal
macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600
or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd
pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with
LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a
prostaglandin H synthase (PHS) inhibitor that has been shown to prevent
BZ-induced myelotoxic and genotoxic effects in mice when coadministered
with benzene were able to convert the pre-IL-1 alpha to mature cytokine.
Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice
before a dose of BZ that causes severe depression of BM cellularity
completely prevents BM depression, most probably by bypassing the inability
of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha
to the mature cytokine.
Volume 78,
Issue 4,
pp. 938-944,
08/15/1991
Copyright © 1991 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S Wilbur, D Wohlers, S Paikoff, L. Keith, and O Faroon
ATSDR evaluation of health effects of benzene and relevance to public health
Toxicology and Industrial Health,
June 1, 2008;
24(5-6):
263 - 398.
[Abstract]
[PDF]
|
|
|
|
|
|
|
Q. Lan, L. Zhang, M. Shen, M. T. Smith, G. Li, R. Vermeulen, S. M. Rappaport, M. S. Forrest, R. B. Hayes, M. Linet, et al.
Polymorphisms in Cytokine and Cellular Adhesion Molecule Genes and Susceptibility to Hematotoxicity among Workers Exposed to Benzene
Cancer Res.,
October 15, 2005;
65(20):
9574 - 9581.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chen
Animal Models for Acquired Bone Marrow Failure Syndromes
Clin. Med. Res.,
May 1, 2005;
3(2):
102 - 108.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Hazel, C Baum, and G. Kalf
Hydroquinone, a bioreactive metabolite of benzene, inhibits apoptosis in myeloblasts
Stem Cells,
November 1, 1996;
14(6):
730 - 742.
[Abstract]
|
|
|
|
|
