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大鼠腹腔注射脂溶性CdSe/ZnS量子点的遗传毒性

Genotoxicity of intraperitoneal injection of lipoamphiphile CdSe/ZnS quantum dots in rats.

作者信息

Aye Mélanie, Di Giorgio Carole, Mekaouche Mourad, Steinberg Jean-Guillaume, Brerro-Saby Christelle, Barthélémy Philippe, De Méo Michel, Jammes Yves

机构信息

UMR MD2 (Dysoxia-Hyperactivity), Aix-Marseille Université, Faculté de Médecine, Marseille, France; Laboratoire de Mutagenèse et Toxicologie Environnementales, Institut Méditerranéen de Biodiversité et d'Ecologie, Aix-Marseille Université, Faculté de Pharmacie, Marseille, France.

出版信息

Mutat Res Genet Toxicol Environ Mutagen. 2013 Dec 12;758(1-2):48-55. doi: 10.1016/j.mrgentox.2013.09.004. Epub 2013 Sep 20.

DOI:10.1016/j.mrgentox.2013.09.004
PMID:24055877
Abstract

The main objective of the present in vivo rat study was to determine the genotoxicity of lipoamphiphile-coated CdSe/ZnS Quantum Dots (QDs), in several organs (brain, liver, kidneys, lungs and testicles). The second objective was to establish the correlations between the QDs genotoxic activity and the oxidative stress, the production of a proinflammatory cytokine (TNF-α), a stress-induced chaperone protein, the phosphorylated heat shock protein 70 (pHsp70), and an increase in the caspase-3 apoptosis factor. Four QDs doses were injected into the peritoneal cavity (5, 5×10(-1), 5×10(-2) and 5×10(-3)μg/kg). DNA lesions in the different organs were measured by the comet assay, and chromosome abnormalities were evaluated by the micronucleus assay on blood reticulocytes (MNRET). Twenty-four hours after the QDs injection, genotoxic effects were observed in the brain and liver and, only for the highest QDs concentration, in testicles. No genotoxic effect was seen in the kidney and lung. The MNRET test revealed a dose-response induction of micronuclei. In parallel, we did neither reveal oxidative stress nor significant variations of TNF-α, pHsp70, and caspase-3. In conclusion, the QDs exerted significant genotoxic effects in the brain and liver, even in the absence of any associated oxidative stress and inflammatory processes.

摘要

本次大鼠体内研究的主要目的是确定脂质两亲物包覆的CdSe/ZnS量子点(QDs)在多个器官(脑、肝、肾、肺和睾丸)中的遗传毒性。第二个目的是建立量子点遗传毒性活性与氧化应激、促炎细胞因子(TNF-α)的产生、应激诱导伴侣蛋白、磷酸化热休克蛋白70(pHsp70)以及半胱天冬酶-3凋亡因子增加之间的相关性。将四种量子点剂量注入腹腔(5、5×10⁻¹、5×10⁻²和5×10⁻³μg/kg)。通过彗星试验测量不同器官中的DNA损伤,并通过网织红细胞微核试验(MNRET)评估染色体异常。量子点注射24小时后,在脑和肝中观察到遗传毒性作用,仅在最高量子点浓度下,在睾丸中观察到遗传毒性作用。在肾和肺中未观察到遗传毒性作用。MNRET试验显示微核呈剂量反应性诱导。同时,我们既未发现氧化应激,也未发现TNF-α、pHsp70和半胱天冬酶-3有显著变化。总之,即使在没有任何相关氧化应激和炎症过程的情况下,量子点在脑和肝中也产生了显著的遗传毒性作用。

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