Cytotoxicity, apoptosis, and in vitro DNA damage induced by potassium chromate
Cytotoxicity, apoptosis, and in vitro DNA damage induced by potassium chromate
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DOI：
10.1006/taap.1999.8779
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发表时间：
1999-11-15
影响因子：
3.8
通讯作者：
Pérez, JM
中科院分区：
文献类型：
--
作者：
Flores, A;Pérez, JM
Cr 6+是一种已知的人类细胞毒性和致癌剂，需要细胞内还原才能激活。我们分析了K_2CrO_4（Cr ~（6+））的细胞毒性和DNA结合特性，并与Cl_3Cr（Cr ~（3+））进行了比较。结果表明，K2 CrO 4在几种人和小鼠细胞系中表现出比Cl 3Cr更高的细胞毒性。K2 CrO 4的细胞毒性活性还表现为能够通过H-ras癌基因转化的顺铂耐药细胞的凋亡产生细胞杀伤。此外，体外DNA结合实验表明，在抗坏血酸（Cr 6+的主要细胞内还原剂）的存在下，K2 CrO 4诱导两个链间交联和链断裂。由于铬酸根阴离子本身对DNA不反应，这些数据表明，K2 CrO 4的细胞毒性可能与Cr 6+还原产生的反应性中间铬物种的DNA结合有关。(C)北京：科学出版社.
Cr6+ is a known human cytotoxic and carcinogenic agent that requires intracellular reduction for activation. We have analyzed the cytotoxic and DNA binding properties of K2CrO4 (Cr6+) in comparison with those of Cl3Cr (Cr3+). The results indicate that K2CrO4 exhibits higher cytotoxicity than Cl3Cr in several human and murine cell lines. The cytotoxic activity of K2CrO4 is also indicated by the fact that is able to produce cell killing through apoptosis in cisplatin-resistant cells transformed by H-ras oncogene. Moreover, in vitro DNA binding experiments show that, in the presence of ascorbate (the major intracellular reductant of Cr6+), K2CrO4 induces both interstrand cross-links and strand breaks. Because the chromate anion is by itself unreactive toward DNA, these data suggest that the cytotoxicity of K2CrO4 may be associated with the DNA binding of reactive intermediate chromium species resulting from reduction of Cr6+. (C) 1999 Academic Press.