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N-氯代氨基酸介导次氯酸盐对 A549 肺癌细胞的作用。

N-Chloroamino acids mediate the action of hypochlorite on A549 lung cancer cells in culture.

机构信息

Department of Molecular Biophysics, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland.

出版信息

Toxicology. 2010 Apr 11;270(2-3):112-20. doi: 10.1016/j.tox.2010.02.003. Epub 2010 Feb 10.

Abstract

Hypochlorous acid, a chlorinating and oxidative agent, has been reported to be implicated in many pathologies. Its markers were found under inflammatory conditions and, at least some of it reveals biological activity. Thus, in this paper we examined whether N-chloroamino acids may act as mediators of the action of hypochlorous acid in cell culture. N-Chloroamino acids were found to possess lower oxidative capacity than HOCl/OCl(-) just after addition to the growth medium. However, all the chlorocompounds studied were cytotoxic to A549 cells, induced a dose-dependent increase in the G(0)/G(1) fraction with simultaneous reduction in the G(2)/M fraction, collapse of the mitochondrial potential and caspase-dependent apoptosis. The content of cellular thiols decreased after 1-h incubation with the chlorocompounds studied. Although amino acids act as scavengers of hypochlorite in plasma, the chlorinated products formed stay reactive and the pattern of their action on cells in vitro is similar to that of hypochlorite.

摘要

次氯酸是一种氯化和氧化试剂,据报道与许多病理学有关。在炎症条件下发现了其标志物,其中至少有一些显示出生物活性。因此,在本文中,我们研究了 N-氯代氨基酸是否可以作为次氯酸在细胞培养中的作用的介质。发现 N-氯代氨基酸在添加到生长培养基中后,其氧化能力低于 HOCl/OCl(-)。然而,所有研究的氯化合物对 A549 细胞均具有细胞毒性,诱导 G(0)/G(1) 分数呈剂量依赖性增加,同时 G(2)/M 分数减少,线粒体电势崩溃和 caspase 依赖性细胞凋亡。用研究的氯化合物孵育 1 小时后,细胞内巯基含量降低。尽管氨基酸在血浆中作为次氯酸盐的清除剂,但形成的氯化产物仍然具有反应性,其在体外对细胞的作用模式与次氯酸盐相似。

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