INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, F-31027 Toulouse, France.
Mutat Res. 2012 Oct 9;748(1-2):8-16. doi: 10.1016/j.mrgentox.2012.05.014. Epub 2012 Jun 26.
Consumers are exposed daily to several pesticide residues in food, which can be of potential concern for human health. Based on a previous study dealing with exposure of the French population to pesticide residues via the food, we selected 14 pesticides frequently found in foodstuffs, on the basis of their persistence in the environment or their bioaccumulation in the food chain. In a first step, the objective of this study was to investigate if the 14 selected pesticides were potentially cytotoxic and genotoxic. For this purpose, we used a new and sensitive genotoxicity assay (the γH2AX test, involving phosphorylation of histone H2AX) with four human cell lines (ACHN, SH-SY5Y, LS-174T and HepG2), each originating from a potential target tissue of food contaminants (kidney, nervous system, colon, and liver, respectively). Tebufenpyrad was the only compound identified as genotoxic and the effect was only observed in the SH-SY5Y neuroblastoma cell-line. A time-course study showed that DNA damage appeared early after treatment (1h), suggesting that oxidative stress could be responsible for the induction of γH2AX. In a second step, three other pesticides were studied, i.e. bixafen, fenpyroximate and tolfenpyrad, which - like tebufenpad - also had a methyl-pyrazole structure. All these compounds demonstrated genotoxic activity in SH-SY5Y cells at low concentration (nanomolar range). Complementary experiments demonstrated that the same compounds show genotoxicity in a human T-cell leukemia cell line (Jurkat). Moreover, we observed an increased production of reactive oxygen species in Jurkat cells in the presence of the four methyl-pyrazoles. These results demonstrate that tebufenpyrad, bixafen, fenpyroximat and tolfenpyrad induce DNA damage in human cell lines, very likely by a mode of action that involves oxidative stress. Nonetheless, additional in vivo data are required before a definitive conclusion can be drawn regarding hazard prediction to humans.
消费者每天都会在食物中接触到几种农药残留，这些残留可能对人类健康造成潜在威胁。基于之前一项研究涉及法国人通过食物接触农药残留的情况，我们选择了 14 种在食品中经常发现的农药，这些农药的选择依据是它们在环境中的持久性或在食物链中的生物累积性。在第一步中，本研究的目的是调查这 14 种选定的农药是否具有潜在的细胞毒性和遗传毒性。为此，我们使用了一种新的、敏感的遗传毒性检测方法（γH2AX 检测法，涉及组蛋白 H2AX 的磷酸化），检测了四种人类细胞系（ACHN、SH-SY5Y、LS-174T 和 HepG2），这四种细胞系分别来源于食品污染物的潜在靶组织（肾脏、神经系统、结肠和肝脏）。 Tebufenpyrad 是唯一被鉴定为具有遗传毒性的化合物，其作用仅在 SH-SY5Y 神经母细胞瘤细胞系中观察到。时间进程研究表明，DNA 损伤在治疗后 1 小时内就出现了，这表明氧化应激可能是诱导 γH2AX 的原因。在第二步中，我们研究了另外三种农药，即 bixafen、fenpyroximate 和 tolfenpyrad，它们与 Tebufenpyrad 一样，也具有甲基吡唑结构。所有这些化合物在低浓度（纳摩尔范围内）时在 SH-SY5Y 细胞中表现出遗传毒性。补充实验表明，相同的化合物在人类 T 细胞白血病细胞系（Jurkat）中也具有遗传毒性。此外，我们观察到在存在四种甲基吡唑的情况下 Jurkat 细胞中活性氧的产生增加。这些结果表明 Tebufenpyrad、bixafen、fenpyroximat 和 tolfenpyrad 诱导了人类细胞系的 DNA 损伤，很可能是通过一种涉及氧化应激的作用模式。尽管如此，在对人类进行危险预测方面得出明确结论之前，还需要更多的体内数据。
