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揭示苯对造血干细胞产生毒性作用机制

  1. 1,4-苯醌
  2. 白血病
  3. 血细胞
  4. 造血干细胞
  5. 造血祖细胞

来源:生物谷 2016-07-04 08:08

在一项新的研究中,马来西亚科学家提供证据证实一种广泛使用的化学物---苯---要比其他的化学物对骨髓中的造血干细胞和造血祖细胞具有更强的毒性。

2016年7月4日/生物谷BIOON/--在一项新的研究中,马来西亚科学家提供证据证实一种广泛使用的化学物要比其他的化学物对骨髓中的造血干细胞和造血祖细胞具有更强的毒性。

苯是世界上最为广泛使用的化学物之一。它主要用于制造塑料、橡胶、染料、去污剂和杀虫剂等材料。它也能够在汽车尾气和工业烟气中发现到。它对血细胞的毒性作用已得到很好地记载,而且已知它导致不同类型的白血病、多发性骨髓瘤和非霍奇金淋巴瘤。然而,关于它的毒性作用的精确机制在此之前人们并不清楚。

在这项研究中,来自马来西亚国民大学的研究人员基于之前的研究,证实苯是在肝脏中进行代谢的,随后它的代谢物在骨髓中经过进一步代谢后产生1,4-苯醌(1,4-benzoquinone, 缩写为1,4-BQ),其中已知1,4-BQ对血细胞是有毒性的。

研究人员在小鼠体内研究了1,4-BQ对造血干细胞(HSC)和造血祖细胞(haematopoietic progenitor cell, HPC)的影响,其中HSC是在骨髓中发现的,能够产生任何一种类型的血细胞,而骨髓中的每种HPC能够分化为仅仅一种特定类型的血细胞。

研究人员让小鼠中的这些骨髓细胞接触不同浓度的1,4-BQ,结果发现它诱导细胞毒性,从而导致自杀性细胞死亡,或者说细胞凋亡。他们也发现相比于T细胞淋巴祖细胞(T cell lymphoid progenitor),1,4-BQ对HSC、髓样祖细胞(myeloid progenitor,能够产生红细胞和血小板等)和B细胞淋巴祖细胞(B cell lymphoid progenitor)的毒性更大。他们也发现1,4-BQ对产生单种血细胞的造血祖细胞的毒性要比产生多种血细胞的造血祖细胞更大。

研究人员说,在此之前还没有一项研究比较过1,4-BQ暴露对不同造血祖细胞的毒性作用。

尽管苯本身可能对血细胞是没有毒性的,但是科学家们认为它的代谢物是有毒性的。研究人员说,这项研究提供一种实验性系统进一步理解苯代谢物如何破坏对造血干细胞的调节。(生物谷 Bioon.com)

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Common chemical highly toxic to blood cell precursors

Benzene is among the most widely used chemicals in the world. It is mainly used to make materials such as plastics, rubbers, dyes, detergents and pesticides. It can also be found in automobile and industrial fumes. Its toxic effects on blood cells are well documented and it’s known to cause different kinds of leukaemia, multiple myeloma and non-Hodgkin lymphoma. However, the exact mechanisms involved in its toxicity are not yet understood.

Researchers from Universiti Kebangsaan Malaysia built on previous research that shows that benzene is metabolized in the liver, then its metabolites are further metabolized in the bone marrow to produce 1,4-benzoquinone (1,4-BQ), which is known for its toxic effects on blood cells. The team studied the effects of 1,4-BQ on “haematopoietic stem cells” (HSCs are stem cells found in the bone marrow that can give rise to any kind of blood cell) and “haematopoietic progenitor cells” (each HPC in the bone marrow can differentiate into only one specific type of blood cell) in mice.

The researchers exposed mouse bone marrow cells to different concentrations of 1,4-BQ and found it induced cytotoxicity that leads to suicidal cell death, or apoptosis. They also found that 1,4-BQ was more toxic to HSCs, myeloid progenitors (which give rise to red blood cells and platelets, among others) and B cell lymphoid progenitors than it was to T cell lymphoid progenitors. They also found that 1,4-BQ was more toxic to progenitors that give rise to a single group of blood cells than it was to progenitors that give rise to multiple groups.

No studies to-date have compared the toxic effects of 1,4-BQ exposure on different haematopoietic progenitors, the researchers say.

Although benzene itself is not likely to be toxic to blood cells, scientists believe its metabolites are. This study provides an experimental system to further understand how benzene metabolites impair the regulation of haematopoietic stem cells, the researchers say.

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会议详情: http://www.bioon.com/z/2016stemcell/

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