Kinetics of granulocytic and erythroid progenitor cells are affected differently by short-term, low-level benzene exposure.
Kinetics of granulocytic and erythroid progenitor cells are affected differently by short-term, low-level benzene exposure.
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短期、低水平的苯暴露对粒细胞和红系祖细胞的动力学产生不同的影响。
DOI：
10.1007/bf01973716
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发表时间：
1991
影响因子：
6.1
通讯作者：
Snyder,CA
中科院分区：
文献类型：
--
作者：
Dempster,AM;Snyder,CA
在之前的工作中，我们确定粒细胞 (CFU-GM) 和红细胞 (CFU-E) 祖细胞群对短期苯暴露表现出不同的反应。我们现在报告调查这些观察到的不同反应的可能机制的工作。将小鼠暴露于空气或 10 ppm 苯中 6 小时/天 X 5 天。最后一次暴露后，立即对小鼠进行注射，即。 v.，用盐水或羟基脲(HU)。 HU的剂量足以杀死细胞周期S期或接近S期的造血细胞，并且足以同步存活的造血细胞群。苯暴露三天后，CFU-E 数量下降至对照值的 50%，而此时 CFU-GM 数量等于对照值。苯暴露足以使 S 期 CFU-E 的百分比增加一倍，但 CFU-GM 没有产生这种增加。在从苯暴露和 HU 处理恢复的 3 天内，CFU-E 群体扩大了 30 倍，而 CFU-GM 群体扩大了不到 3 倍。在苯暴露和 HU 处理后，两种祖细胞产生的各自后代数量均有所增加。当苯暴露小鼠的 CFU-E 与不同浓度的促红细胞生成素 (EPO) 一起培养时，最大 EPO 浓度下的反应是对照 CFU-E 反应的 66%。这强烈表明接触苯的小鼠的 CFU-E 群体中处于或接近 S 期的细胞已被耗尽。结果表明，CFU-GM 通过增加其分化率而不是其增殖率来响应低水平苯暴露，而 CFU-E 通过增加其分化率和增殖率来响应。我们推测，CFU-E 增殖的增加使得这些细胞比粒细胞细胞更容易受到苯的影响，特别是那些处于或接近细胞周期 S 期的 CFU-E。
In previous work, we determined that granulocytic (CFU-GM) and erythroid (CFU-E) progenitor cell populations exhibited disparate responses to short-term benzene exposures. We now report on work investigating possible mechanisms for these observed disparate responses. Mice were exposed to either air or 10 ppm benzene for 6 h/d X 5 d. Immediately after the last exposure, mice were injected, i. v., with either saline or hydroxyurea (HU). The dose of HU was sufficient to kill hematopoietic cells in or near S-phase of the cell cycle and sufficient to synchronize the surviving populations of hematopoietic cells. Three days after benzene exposure, CFU-E numbers had declined to 50% of control values while CFU-GM numbers were equal to control values at this time. The benzene exposures were sufficient to double the percentage of CFU-E in S-phase but produced no such increase among CFU-GM. During 3 days of recovery from benzene exposure and HU treatment, the CFU-E population expanded 30-fold while the CFU-GM population expanded less than 3-fold. Following benzene exposure and HU treatment, both progenitor cells produced elevated numbers of their respective progeny. When CFU-E from benzene-exposed mice were cultured with varying concentrations of erythropoietin (EPO), the response at maximal EPO concentration was 66% of the response by control CFU-E. This strongly suggests that the CFU-E populations from benzene-exposed mice had been depleted of cells in or near S-phase. The results indicate that CFU-GM respond to low-level benzene exposure by increasing their rate of differentiation but not their rate of proliferation, while CFU-E respond by increasing both their rates of differentiation and proliferation. We speculate that it is the increase in CFU-E proliferation that renders these cells more susceptible to benzene than their granulocytic counterparts, especially those CFU-E at or near the S-phase of the cell cycle.