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Hydroquinone stimulates granulocyte-macrophage progenitor cells in vitro and in vivo
R Henschler1, H R Glatt, C M Heyworth
1Department of Hematology/Oncology, Freiburg University Medical Center, Federal Republic of Germany.
Abstract:
To investigate whether hydroxylated metabolites of benzene may be responsible for the amplification of granulocyte-macrophage progenitor cells (GM-CFC) observed in mice that inhale benzene, groups of six C57BL6 mice were injected with hydroquinone (HQ) (75 mg/kg) or HQ (50 mg/kg) plus phenol (PHE) (50 mg/kg) twice daily for 11 days. Deviations in blood leukocyte and erythrocyte levels by up to one-third were noted in the treated groups; however, the peripheral blood differential counts were unchanged. Although no changes in bone marrow cellularity were observed in mice treated with HQ, cellularity was decreased by a factor of two in the mice that had received HQ plus PHE. The number of GM-CFC per femur was doubled in both treated groups. In vitro experiments using the murine multipotent hematopoietic progenitor cells FDCP mix also showed a duplication of GM-CFC formation in the presence of HQ at concentrations between 10(-6) M and 10(-10) M. When HQ and PHE were present at equimolar concentrations, significantly increased colony formation was still observed with 10(-12) M of metabolites. The effect was independent of the concentration of GM-colony-stimulating factor used. We suggest that HQ is a major mediator of the stimulatory effect of benzene on GM-CFC in mice. In addition, the in vitro data indicate that a direct effect of GM-CFC is involved.
Insights
Hydroquinone (HQ), a benzene metabolite, significantly amplifies granulocyte-macrophage progenitor cells (GM-CFC) in mice. This study suggests HQ directly stimulates GM-CFC, impacting hematopoietic progenitor cells.
Area of Science:
- Toxicology
- Hematology
- Cell Biology
Background:
- Benzene inhalation can alter blood cell levels.
- Hydroxylated benzene metabolites are suspected mediators of these effects.
- Granulocyte-macrophage progenitor cells (GM-CFC) are key targets in hematopoiesis.
Purpose of the Study:
- To determine if hydroquinone (HQ) and phenol (PHE), benzene metabolites, amplify GM-CFC in mice.
- To investigate the direct effect of HQ and PHE on hematopoietic progenitor cells in vitro.
- To identify the primary mediator of benzene's stimulatory effect on GM-CFC.
Main Methods:
- Mice were injected with hydroquinone (HQ) or HQ plus phenol (PHE).
- Blood leukocyte and erythrocyte levels, and bone marrow cellularity were analyzed.
- In vitro experiments used murine multipotent hematopoietic progenitor cells (FDCP mix) with varying concentrations of HQ and PHE.
- GM-CFC formation was assessed in the presence of metabolites and GM-colony-stimulating factor.
Main Results:
- Mice treated with HQ or HQ plus PHE showed a doubling of GM-CFC per femur.
- Bone marrow cellularity decreased in mice treated with HQ plus PHE.
- In vitro, HQ significantly increased GM-CFC formation across a range of concentrations (10^-6 M to 10^-10 M).
- Increased colony formation was observed even at 10^-12 M equimolar concentrations of HQ and PHE.
Conclusions:
- Hydroquinone (HQ) is a major mediator of benzene's stimulatory effect on mouse GM-CFC.
- The in vitro data suggest a direct stimulatory effect of HQ on GM-CFC.
- Benzene metabolites, particularly HQ, play a significant role in modulating hematopoietic progenitor cell activity.