Henschler R, Glatt H R, Heyworth C M
Department of Hematology/Oncology, Freiburg University Medical Center, Federal Republic of Germany.
Environ Health Perspect. 1996 Dec;104 Suppl 6(Suppl 6):1271-4. doi: 10.1289/ehp.961041271.
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.
为了研究苯的羟基化代谢产物是否可能是导致吸入苯的小鼠中粒细胞-巨噬细胞祖细胞(GM-CFC)扩增的原因,将每组6只C57BL6小鼠每天注射对苯二酚(HQ)(75毫克/千克)或HQ(50毫克/千克)加苯酚(PHE)(50毫克/千克)两次,持续11天。在处理组中发现血液白细胞和红细胞水平偏差高达三分之一;然而,外周血分类计数没有变化。虽然用HQ处理的小鼠骨髓细胞密度没有观察到变化,但接受HQ加PHE的小鼠细胞密度降低了两倍。两个处理组中每根股骨的GM-CFC数量都增加了一倍。使用小鼠多能造血祖细胞FDCP mix进行的体外实验也表明,在浓度介于10(-6)M和10(-10)M之间的HQ存在下,GM-CFC形成增加了一倍。当HQ和PHE以等摩尔浓度存在时,用10(-12)M的代谢产物仍观察到显著增加的集落形成。该效应与所用GM集落刺激因子的浓度无关。我们认为HQ是苯对小鼠GM-CFC刺激作用的主要介质。此外,体外数据表明涉及GM-CFC的直接作用。