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T-2 毒素和脱氧雪腐镰刀菌烯醇对人 C-28/I2 细胞和大鼠原代软骨细胞的单独及联合毒性作用。

Individual and combined toxicity of T-2 toxin and deoxynivalenol on human C-28/I2 and rat primary chondrocytes.

机构信息

Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.

Xi'an Hong Hui Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, 710054, China.

出版信息

J Appl Toxicol. 2019 Feb;39(2):343-353. doi: 10.1002/jat.3725. Epub 2018 Sep 25.

Abstract

Deoxynivalenol (DON) and T-2 toxin are prevalent mycotoxin contaminants in the food and feed stuffs worldwide, with non-negligible co-contamination and co-exposure conditions. Meanwhile, they are considerable risk factors for Kashin-Beck disease, a chronic endemic osteochondropathy. The aim of this study was to investigate the individual and combined cytotoxicity of DON and T-2 toxin on proliferating human C-28/I2 and newborn rat primary costal chondrocytes by MTT assay. Four molar concentration combination ratios of DON and T-2 toxin were used, 1:1 for R1 mixture, 10:1 for R10, 100:1 for R100 and 1000:1 for R1000. The toxicological interactions were quantified by the MixLow method. DON, T-2 toxin, and their mixtures all showed a clear dose-dependent toxicity for chondrocytes. The cytotoxicity of T-2 toxin was 285-fold higher than DON was in human chondrocytes, and 22-fold higher in the rat chondrocytes. The combination of DON and T-2 toxin was significantly synergistic at middle and high level concentrations of R10 mixtures in rat chondrocytes, but significantly antagonistic at the low concentrations of R100 mixtures in both cells and at the middle concentrations of R1000 mixtures in rat chondrocytes. These results indicated that the combined toxicity was influenced by the cell sensitivity for toxins, the difference between the combination ratio and equitoxic ratio, the concentrations and other factors.

摘要

脱氧雪腐镰刀菌烯醇(DON)和 T-2 毒素是全球食品和饲料中普遍存在的真菌毒素污染物,存在不可忽视的共同污染和共同暴露情况。同时,它们也是慢性地方性骨关节病——大骨节病的重要危险因素。本研究旨在通过 MTT 法研究 DON 和 T-2 毒素对增殖的人 C-28/I2 和新生大鼠原代肋软骨细胞的单独和联合细胞毒性。使用了 DON 和 T-2 毒素的四个摩尔浓度组合比例,R1 混合物为 1:1,R10 为 10:1,R100 为 100:1,R1000 为 1000:1。采用 MixLow 法量化了毒理学相互作用。DON、T-2 毒素及其混合物对软骨细胞均表现出明显的剂量依赖性毒性。T-2 毒素对人软骨细胞的细胞毒性比 DON 高 285 倍,对大鼠软骨细胞的细胞毒性高 22 倍。在大鼠软骨细胞中,R10 混合物的中高浓度下,DON 和 T-2 毒素的组合具有明显的协同作用,但在两种细胞的 R100 混合物的低浓度下以及大鼠软骨细胞的 R1000 混合物的中浓度下具有明显的拮抗作用。这些结果表明,联合毒性受细胞对毒素的敏感性、组合比例与等毒性比例的差异、浓度等因素的影响。

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