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硫化镉纳米颗粒的细胞毒性和遗传毒性作用

Cytotoxic and genotoxic effects of cadmium sulfide nanoparticles.

作者信息

Apykhtina О L, Dybkova S M, Sokurenko L M, Chaikovsky Yu B

机构信息

SI "Kundiiev Institute of Occupational Health of the National Academy of Medical Sciences of Ukraine", Kyiv 01033, Ukraine.

F.D. Ovcharenko Institute of Biocolloidal Chemistry, NAN of Ukraine, Kyiv 03142, Ukraine.

出版信息

Exp Oncol. 2018 Oct;40(3):194-199.

Abstract

UNLABELLED

Cadmium compounds are highly toxic substances characterized by mutagenic, genotoxic and carcinogenic effects, and having high cumulative properties. Application of cadmium nanoparticles (NPs) in medicine stimulates the study of their mechanism of action at the cellular level and at the level of organs and systems, determination of biomarkers of their action, particularly in comparison with the ionic form. The aim of the study was to compare the features of cytotoxic and genotoxic effects of cadmium sulfide (CdS) NPs of different sizes on cell cultures of different histogenesis with those of cadmium chloride (CdCl2).

MATERIALS AND METHODS

In this work, we used cadmium compounds in the nanoform: NPs CdS of 4-6 nm and of 9-11 nm in size; and in the ionic form: CdCl2. The studies were conducted in vitro in cell lines - IMR-32, НEК-293 and MАEC. To count viable cells we compared the results of three basic tests: MTT (methyl tetrasolium test), SRB (sulforhodamine B test) and NRU (neutral red uptake test). We evaluated the genotoxic effect of the substances studied in vitro using DNA comet assay in alkaline conditions.

RESULTS

CdS NPs and CdCl2 demonstrated pronounced dose-dependent cytotoxic effect in MАEC, НEК-293 and IMR-32 cell lines, by impairing membrane permeability, functioning of mitochondria and lysosomes, and inhibiting the function of protein synthesis. Cytotoxic effect of CdCl2 was the most pronounced, this effect of CdS NPs of 9-11 nm in size being the least pronounced. The comet DNA assay in alkaline conditions revealed a statistically significant increase in DNA comet index when exposed to CdCl2 and CdS NPs in comparison with the negative control, which indicates their genotoxic effect. CdS NPs of 4-6 nm in size showed a more pronounced effect in comparison with those of 9-11 nm in size.

CONCLUSION

Elucidation of mechanisms underlying the implementation of toxic effects of cadmium NPs will help in assessing the potential risks associated with their use in industry and developing effective preventive measures. For instance, when planning in vivo studies for toxicological evaluation of nanomaterials and nano-substances containing NPs of cadmium, it is necessary to investigate the mutagenic and carcinogenic risks and to take into account the high likelihood of neurotoxic and cardiovasotoxic effects, along with nephrotoxic effects, since high cytotoxic activity of the investigated compounds of cadmium was detected on the cells of the MАEC line (endothelial origin) and IMR-32 (neuronal origin).

摘要

未标注

镉化合物是剧毒物质,具有致突变、基因毒性和致癌作用,且具有高累积特性。镉纳米颗粒(NPs)在医学上的应用激发了对其在细胞水平以及器官和系统水平上作用机制的研究,确定其作用的生物标志物,特别是与离子形式进行比较。本研究的目的是比较不同尺寸的硫化镉(CdS)纳米颗粒与氯化镉(CdCl2)对不同组织发生来源的细胞培养物的细胞毒性和基因毒性作用特征。

材料与方法

在本研究中,我们使用了纳米形式的镉化合物:尺寸为4 - 6纳米和9 - 11纳米的CdS纳米颗粒;以及离子形式的:CdCl2。研究在体外细胞系 - IMR - 32、HEK - 293和MAEC中进行。为了计数活细胞,我们比较了三种基本测试的结果:MTT(甲基四氮唑试验)、SRB(磺酰罗丹明B试验)和NRU(中性红摄取试验)。我们使用碱性条件下的DNA彗星试验评估所研究物质在体外的基因毒性作用。

结果

CdS纳米颗粒和CdCl2在MAEC、HEK - 293和IMR - 32细胞系中表现出明显的剂量依赖性细胞毒性作用,通过损害膜通透性、线粒体和溶酶体功能以及抑制蛋白质合成功能。CdCl2的细胞毒性作用最为明显,尺寸为9 - 11纳米的CdS纳米颗粒的这种作用最不明显。碱性条件下的彗星DNA试验显示,与阴性对照相比,暴露于CdCl2和CdS纳米颗粒时DNA彗星指数有统计学显著增加,这表明它们具有基因毒性作用。尺寸为4 - 6纳米的CdS纳米颗粒比尺寸为9 - 11纳米的表现出更明显的作用。

结论

阐明镉纳米颗粒毒性作用的潜在机制将有助于评估与其在工业中使用相关的潜在风险,并制定有效的预防措施。例如,在规划对含有镉纳米颗粒的纳米材料和纳米物质进行毒理学评估的体内研究时,有必要研究诱变和致癌风险,并考虑到神经毒性和心血管毒性作用以及肾毒性作用的高可能性,因为在所研究的镉化合物对MAEC系(内皮来源)和IMR - 32(神经来源)细胞具有高细胞毒性活性。

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