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霉菌毒素脱氧雪腐镰刀菌烯醇在细菌以及人类TK6和HepaRG细胞系中无体外遗传毒性潜力。

Absence of in vitro genotoxicity potential of the mycotoxin deoxynivalenol in bacteria and in human TK6 and HepaRG cell lines.

作者信息

Takakura Natsuko, Nesslany Fabrice, Fessard Valérie, Le Hegarat Ludovic

机构信息

ANSES, French Agency for Food, Environmental and Occupational Health & Safety, Fougères Laboratory, Toxicology of Contaminants Unit, Fougères, France.

Institut Pasteur de Lille, Laboratory of Toxicology, EA 4483 Lille, France.

出版信息

Food Chem Toxicol. 2014 Apr;66:113-21. doi: 10.1016/j.fct.2014.01.029. Epub 2014 Jan 24.

DOI:10.1016/j.fct.2014.01.029
PMID:24468671
Abstract

Deoxynivalenol (DON) is the major mycotoxin detected in cereal foods and a risk for human health following DON ingestion could not be excluded due to high level exposure. In this light, the hazard of DON must be carefully evaluated. Therefore, the aim of this study is to perform in vitro genotoxicity tests with DON using the Salmonella typhimurium reverse mutation assay (Ames' test), the comet assay and the micronucleus test in accordance with the OECD test guideline 487 in two human cell lines: the lymphoblastoid TK6 and the hepatoma HepaRG cells. DON gave negative results in the Ames' test performed, both with and without rat liver S9 on three strains TA98, TA100 and TA102. DON elicited cytotoxicity in TK6 and HepaRG cells but did not induce primary DNA damage. DON failed also to induce MN formation in TK6 cells with or without human and rat liver S9. After 24h of treatment, DON induced micronucleus formation in TK6 cells but only at concentrations producing more than 55 ± 5% cytotoxicity. In HepaRG cells, DON highly increased the caspase-3/7 activity but no micronucleus induction was observed. Taken together, our results suggest that DON could be considered as a non in vitro genotoxin.

摘要

脱氧雪腐镰刀菌烯醇(DON)是谷物食品中检测到的主要霉菌毒素,由于接触水平较高,不能排除摄入DON后对人类健康造成风险。鉴于此,必须仔细评估DON的危害。因此,本研究的目的是根据经合组织测试指南487,在两种人类细胞系:淋巴母细胞TK6和肝癌HepaRG细胞中,使用鼠伤寒沙门氏菌回复突变试验(艾姆斯试验)、彗星试验和微核试验对DON进行体外遗传毒性测试。在对TA98、TA100和TA102三种菌株进行的艾姆斯试验中,无论有无大鼠肝脏S9,DON均给出阴性结果。DON在TK6和HepaRG细胞中引起细胞毒性,但未诱导原发性DNA损伤。无论有无人类和大鼠肝脏S9,DON在TK6细胞中也未能诱导微核形成。处理24小时后,DON在TK6细胞中诱导微核形成,但仅在产生超过55±5%细胞毒性的浓度下。在HepaRG细胞中,DON显著增加了caspase-3/7活性,但未观察到微核诱导。综上所述,我们的结果表明DON可被视为一种非体外基因毒素。

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