Li Yuzhe, Zhang Boyang, He Xiaoyun, Cheng Wen-Hsing, Xu Wentao, Luo Yunbo, Liang Rui, Luo Haoshu, Huang Kunlun
Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, MS 39762, USA.
Toxins (Basel). 2014 Mar 26;6(4):1177-92. doi: 10.3390/toxins6041177.
Ochratoxin A (OTA) and Zearalenone (ZEA) are widespread mycotoxins that contaminate foodstuffs simultaneously, but sufficient data regarding their mixed toxicities are lacking. This study aims to analyze the style of combined effects of OTA and ZEA on cells of their target organs. For this purpose, cytotoxicity was determined in HepG2 and KK-1 cells treated with single and combined forms of OTA and ZEA. Furthermore, we have analyzed the data using two mathematical models based on the concepts of concentration addition (CA) and independent addition (IA). By analyzing data with nonlinear regression, toxins applied singly showed classic sigmoid dose-response curves in HepG2 cells whereas in KK-1 cells hormetic responses were observed. Exposure to equieffective mixtures of OTA and ZEA showed additive effects, irrespective of different nonlinear regression models used. Our results demonstrate that IA is an appropriate concept to account for mixture effects of OTA and ZEA. The results in ROS generation indicate a departure from additivity to antagonism or synergism at different concentrations, probably due to potential interaction during ROS production. This study shows that a risk assessment of mycotoxins should account for mixture effects, and prediction models are valuable tools for mixture assessment.
赭曲霉毒素A（OTA）和玉米赤霉烯酮（ZEA）是广泛存在的霉菌毒素，它们会同时污染食品，但关于它们混合毒性的充分数据却很缺乏。本研究旨在分析OTA和ZEA对其靶器官细胞的联合作用方式。为此，在用OTA和ZEA的单一形式及联合形式处理的HepG2和KK-1细胞中测定细胞毒性。此外，我们使用基于浓度相加（CA）和独立相加（IA）概念的两个数学模型对数据进行了分析。通过非线性回归分析数据，单独应用的毒素在HepG2细胞中显示出典型的S形剂量反应曲线，而在KK-1细胞中观察到了 hormetic反应。暴露于OTA和ZEA的等效混合物显示出相加效应，无论使用何种不同的非线性回归模型。我们的结果表明，IA是解释OTA和ZEA混合效应的一个合适概念。活性氧生成结果表明，在不同浓度下，从相加性偏离为拮抗或协同作用，这可能是由于活性氧产生过程中的潜在相互作用。本研究表明，霉菌毒素的风险评估应考虑混合效应，预测模型是混合评估的有价值工具。
