Suppr超能文献

对苯二酚对人外周血淋巴细胞的细胞毒性、DNA损伤及细胞遗传学效应的体外评估。

In vitro assessment of the cytotoxic, DNA damaging, and cytogenetic effects of hydroquinone in human peripheral blood lymphocytes.

作者信息

Jurica Karlo, Karačonji Irena Brčić, Benković Vesna, Kopjar Nevenka

机构信息

1Special Security Operations Directorate, Ministry of the Interior, Zagreb, Croatia.

2Institute for Medical Research and Occupational Health, Zagreb, Croatia.

出版信息

Arh Hig Rada Toksikol. 2017 Dec 20;68(4):322-335. doi: 10.1515/aiht-2017-68-3060.

Abstract

This study investigated the mechanisms of hydroquinone toxicity and assessed the relationships between its cytotoxic, genotoxic, and cytogenetic effects tested at 8, 140, and 280 μg mL-1 in human peripheral blood lymphocytes exposed for 24 h. The outcomes of the treatments were evaluated using the apoptosis/necrosis assay, the alkaline comet assay, and the cytokinesis-block micronucleus (CBMN) cytome assay. The tested hydroquinone concentrations produced relatively weak cytotoxicity in resting lymphocytes, which mostly died via apoptosis. Hydroquinone's marked genotoxic effects were detected using the alkaline comet assay. Significantly decreased values of all comet parameters compared to controls indicated specific mechanisms of hydroquinone-DNA interactions. Our results suggest that the two higher hydroquinone concentrations possibly led to cross-linking and adduct formation. Increased levels of DNA breakage measured following exposure to the lowest concentration suggested mechanisms related to oxidative stress and inhibition of topoisomerase II. At 8 μg mL-1, hydroquinone did not significantly affect MN formation. At 140 and 280 μg mL-1, it completely blocked lymphocyte division. The two latter concentrations also led to erythrocyte stabilization and prevented their lysis. At least two facts contribute to this study's relevance: (I) this is the first study that quantifies the degree of reduction in total comet area measured in lymphocyte DNA after hydroquinone treatment, (II) it is also the first one on a lymphocyte model that adopted the "cytome" protocol in an MN assay and found that lymphocytes exposure even to low hydroquinone concentration resulted in a significant increase of nuclear bud frequency. Considering the limitations of the lymphocyte model, which does not possess intrinsic metabolic activation, in order to unequivocally prove the obtained results further studies using other appropriate cell lines are advised.

摘要

本研究调查了对苯二酚毒性的机制,并评估了在人外周血淋巴细胞中分别以8、140和280μg mL-1的浓度暴露24小时后,其细胞毒性、遗传毒性和细胞遗传学效应之间的关系。使用凋亡/坏死检测法、碱性彗星试验和胞质分裂阻滞微核(CBMN)细胞分析法评估处理结果。所测试的对苯二酚浓度在静息淋巴细胞中产生相对较弱的细胞毒性,这些细胞大多通过凋亡死亡。使用碱性彗星试验检测到对苯二酚具有显著的遗传毒性作用。与对照组相比,所有彗星参数值均显著降低,表明对苯二酚与DNA相互作用存在特定机制。我们的结果表明,较高的两个对苯二酚浓度可能导致交联和加合物形成。暴露于最低浓度后测得的DNA断裂水平增加,提示其机制与氧化应激和拓扑异构酶II抑制有关。在8μg mL-1时,对苯二酚对微核形成没有显著影响。在140和280μg mL-1时,它完全阻断了淋巴细胞分裂。后两个浓度还导致红细胞稳定并防止其裂解。至少有两个因素使本研究具有相关性:(I)这是第一项量化对苯二酚处理后淋巴细胞DNA中总彗星面积减少程度的研究,(II)这也是第一项在淋巴细胞模型上采用“细胞组学”方案进行微核试验的研究,并且发现即使淋巴细胞暴露于低浓度的对苯二酚也会导致核芽频率显著增加。考虑到淋巴细胞模型的局限性,即不具备内在的代谢激活能力,为了明确证明所得结果,建议使用其他合适的细胞系进行进一步研究。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验