Permeability, cytotoxicity, and genotoxicity of chromium(V) and chromium(VI) complexes in V79 Chinese hamster lung cells
Permeability, cytotoxicity, and genotoxicity of chromium(V) and chromium(VI) complexes in V79 Chinese hamster lung cells
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DOI：
10.1021/tx9701541
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发表时间：
1998-02-01
影响因子：
4.1
通讯作者：
Kostka, KL
中科院分区：
文献类型：
--
作者：
Dillon, CT;Lay, PA;Kostka, KL
本文首次用体外微核试验研究了铬(V)络合物对哺乳动物细胞(V79中国仓鼠肺细胞)的遗传毒性。研究了两种络合物，[CrO(Ehba)(2)](-)，它在细胞生长介质中进行配体交换和歧化反应，以及[CrO(Manpa)](-)，它在暴露期间在介质中处于化学惰性状态。体外微核试验结果表明，两种配合物均具有遗传毒性，且与[Cr2O7](2-)具有相似的毒性。利用单个细胞的粒子诱导X射线发射(PIXE)分析首次研究了铬(V)络合物的渗透性。铬的吸收顺序为：[cr(Phen)(2-)(H2O)(2)](3+)<；[CrO(Ehba)(2)](-)<；[CrO(Manpa)](-)<；[Cr2O7](2-)。克隆实验表明，铬(VI)具有比铬(V)络合物更高的细胞毒性。虽然铬(V)和铬(VI)络合物的遗传毒性随着其通透性的增加而增加，但就进入细胞的铬的量而言，铬(V)络合物的遗传毒性等于或大于铬(VI)的遗传毒性。这支持了其他证据，即铬(V)作为细胞内铬(VI)还原产生的代谢中间产物，在铬诱导的癌症中可能是重要的。
The genotoxicity of Cr(V) complexes in mammalian cells (V79 Chinese hamster lung cells) has been studied for the first time using the in vitro micronucleus assay. Two complexes were investigated, [CrO(ehba)(2)](-), which undergoes ligand-exchange and disproportionation reactions in the cell growth medium, and [CrO(mampa)](-), which is chemically inert in the medium for the duration of the exposure period. Results of in vitro micronucleus assays show that both complexes are genotoxic and exhibit similar potencies to that of [Cr2O7](2-). The permeabilities of the Cr(V) complexes were also investigated for the first time using particle-induced X-ray emission (PIXE) analysis of individual cells. The Cr uptake increased in the order: [Cr(phen)(2-)(H2O)(2)](3+) < [CrO(ehba)(2)](-) < [CrO(mampa)](-) < [Cr2O7](2-). Clonal assays showed that Cr(VI) exhibits an expectedly higher cytotoxicity than the Cr(V) complexes. While the genotoxicities of the Cr(V) and Cr(VI) complexes increase according to their permeabilities, the genotoxicities of the Cr(V) complexes are equal to, if not greater than, that of Cr(VI) in terms of the amount of Cr entering the cell. This supports other evidence that Cr(V), produced as a metabolic intermediate from the intracellular reduction of Cr(VI), may be important in Cr-induced cancers.