苯诱导白血病可能与对造血干细胞毒性作用有关

2016-07-03 MedSci MedSci原创

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

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。


原始出处:

Chow PW, Abdul Hamid Z, Chan KM, Inayat-Hussain SH, Rajab NF. Lineage-related cytotoxicity and clonogenic profile of 1,4-benzoquinone-exposed hematopoieticstem and progenitor cells. Toxicol Appl Pharmacol. 2015 Apr 1;284(1):8-15.

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    2016-07-04 sillywu

    化学实验室啊

    0

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STM:birinapant和emricasan新的药物组合在治疗白血病上显示成功的希望

急性骨髓白血病(AML)患者,可以期待研发的新疗法。 沃尔特和伊莱扎霍尔研究所的研究人员发现,杀死有害细胞繁殖的新方法。 细胞有一个称为细胞凋亡(程序性细胞死亡)的过程——这是一种自然和必要的反应,以保持人类细胞受控制的增殖。癌细胞,包括AML,是没有这一过程的,结果是细胞不受控制的生长。 由研究所的John Silke教授和墨尔本默多克儿童研究所Paul Ekert教授领导的研究团队,团队

Blood:什么让白血病死灰复燃?

研究人员首次发现,在化疗过程中,某些白血病细胞能获得来自正常细胞的能源资源,从而在治疗后不仅帮助癌细胞生存,而且帮助它们繁荣发展。 这项研究发表在今天的《Blood》杂志,重点是急性髓系白血病(AML)——一种血液和骨髓癌,是在成人中最常见的急性白血病类型。根据美国癌症协会资料显示,在美国每年有近20000名成年人患有AML,另有10400人死于这种疾病。尽管在最初进行化疗通常可成功对抗这种