On the mechanism of genotoxicity of ethephon on embryonic fibroblast cells

IF 2.8 4区医学 Q2 TOXICOLOGY

Toxicology Mechanisms and Methods Pub Date : 2017-01-08 DOI:10.1080/15376516.2016.1273425

M. Hodjat, M. Baeeri, M. Rezvanfar, M. Rahimifard, M. Gholami, M. Abdollahi

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引用次数: 27

Abstract

Abstract Ethephon is one of the most widely used plant growth regulator in agriculture that its application has been increased in recent years. Many reports have raised concern over the safety of this organophosphorus compound. The aim of the current study was to assess the potential genotoxic effect of ethephon on murine embryonic fibroblast (MEF) cell line, using two genotoxicity endpoints: γH2AX expression and comet assay. γH2AX served as an early and sensitive biomarker of genotoxic damage. Oxidative stress biomarkers, including reactive oxygen species (ROS), lipid peroxidation (LPO) and total antioxidant capacity were also examined. The results showed a significant increase in cell proliferation, 24 h post-treatment with 10, 40,160 μg/ml ethephon, while at the higher concentrations cytotoxic effect was observed. The γH2AX expression and γH2AX foci count per cell were significantly increased at non-cytotoxic concentrations of ethephon, accompanied with increased DNA damage as illustrated by comet assay. LPO and ROS levels were elevated only at 160 μg/ml and higher doses. The results interestingly showed that low non-cytotoxic doses of ethephon promoted DNA damage inducing cell proliferation, raising the possibility of ethephon mutagenicity. The genotoxic effect of ethephon at low doses might not relate to oxidative damage and that increased in the level of ROS and LPO generation at higher doses could account for the cytotoxic effect of ethephon. Taken together, our study provides strong in vitro evidence on potential genotoxicity of ethephon at low doses. More precise studies are needed to clarify the mutagenic effect of chronic exposure to ethephon.

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乙烯利对胚胎成纤维细胞遗传毒性机制的研究

摘要乙烯利是近年来应用最广泛的农业植物生长调节剂之一。许多报道对这种有机磷化合物的安全性提出了担忧。本研究的目的是评估乙烯利对小鼠胚胎成纤维细胞（MEF）细胞系的潜在遗传毒性作用，使用两个遗传毒性终点：γH2AX表达和彗星测定。γH2AX是基因毒性损伤的早期和敏感的生物标志物。还检测了氧化应激生物标志物，包括活性氧（ROS）、脂质过氧化（LPO）和总抗氧化能力。结果显示细胞增殖显著增加，24 h用1040160进行后处理 μg/ml乙烯利，而在较高浓度下观察到细胞毒性作用。彗星试验表明，在非细胞毒性浓度的乙烯利下，每个细胞的γH2AX表达和γH2AX病灶数显著增加，同时伴有DNA损伤增加。LPO和ROS水平仅在160 μg/ml及更高剂量。结果有趣地表明，低剂量的非细胞毒性乙烯利促进了DNA损伤诱导的细胞增殖，增加了乙烯利致突变的可能性。低剂量乙烯利的基因毒性作用可能与氧化损伤无关，而高剂量时ROS和LPO生成水平的增加可能是乙烯利的细胞毒性作用的原因。总之，我们的研究为低剂量乙烯利的潜在遗传毒性提供了强有力的体外证据。需要更精确的研究来阐明长期接触乙烯利的诱变作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology Mechanisms and Methods TOXICOLOGY-

自引率

3.10%

发文量

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.