Hydroquinone stimulates granulocyte-macrophage progenitor cells in vitro and in vivo.
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.
Henschler
R
R
Department of Hematology/Oncology, Freiburg University Medical Center, Federal Republic of Germany.
Glatt
H R
HR
Heyworth
C M
CM
D000818:Animals; D001554:Benzene / Q000378:metabolism / Q000633:toxicity; D003114:Colony-Forming Units Assay; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects*; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006873:Hydroquinones / Q000378:metabolism / Q000633:toxicity*; D066298:In Vitro Techniques; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019800:Phenol; D010636:Phenols / Q000378:metabolism / Q000633:toxicity
D006873:Hydroquinones; D010636:Phenols; D019800:Phenol; D001554:Benzene; C031927:hydroquinone