Dillon C T, Lay P A, Bonin A M, Cholewa M, Legge G J, Collins T J, Kostka K L
School of Chemistry, University of Sydney, NSW, Australia.
Chem Res Toxicol. 1998 Feb;11(2):119-29. doi: 10.1021/tx9701541.
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.
首次使用体外微核试验研究了Cr(V)配合物在哺乳动物细胞(V79中国仓鼠肺细胞)中的遗传毒性。研究了两种配合物,[CrO(ehba)2]-,其在细胞生长培养基中会发生配体交换和歧化反应,以及[CrO(mampa)]-,其在暴露期间在培养基中化学性质稳定。体外微核试验结果表明,这两种配合物均具有遗传毒性,且与[Cr2O7]2-表现出相似的效力。还首次使用单细胞粒子诱导X射线发射(PIXE)分析研究了Cr(V)配合物的渗透性。Cr的摄取量按以下顺序增加:[Cr(phen)2-(H2O)2]3+ < [CrO(ehba)2]- < [CrO(mampa)]- < [Cr2O7]2-。克隆试验表明,Cr(VI)表现出比Cr(V)配合物更高的细胞毒性。虽然Cr(V)和Cr(VI)配合物的遗传毒性随其渗透性增加,但就进入细胞的Cr量而言,Cr(V)配合物的遗传毒性即使不大于Cr(VI),也与之相当。这支持了其他证据,即作为Cr(VI)细胞内还原产生的代谢中间体,Cr(V)可能在Cr诱导的癌症中起重要作用。