Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China.
University of Tübingen, BG Trauma Center, Schnarrenbergstr. 95, 72076 Tübingen, Germany.
Food Chem Toxicol. 2014 Feb;64:383-96. doi: 10.1016/j.fct.2013.12.012. Epub 2013 Dec 16.
Deoxynivalenol (DON) is one of the most common mycotoxins. The aim of this study consists in using diverse cellular and molecular assays to evaluate cytotoxicity, genotoxicity as well as oxidative damage and to investigate their mechanisms in human peripheral blood lymphocytes. The human lymphocytes were cultured in eight different doses of DON (0, 6.25, 12.5, 25, 50, 100, 250 and 500 ng/mL) during 6, 12 and 24 h. DON was able to decrease cell viability and cause damage to the membrane, the chromosomes or the DNA at all times of culture. It was also able to induce lipid peroxidation and raise the levels of 8-OHdG and ROS in 6, 12 and 24 h. The results of the RT-PCR and the Western Blot indicated that DON is able to enhance mRNA or protein expressions of DNA repair genes and HO-1 in 6 h and to inhibit these expressions in 24 h. DON potentially triggers genotoxicity in human lymphocytes. This mechanism is probably related to depletion of antioxidase and oxidative damage to the DNA that reduced expression of HO-1, thereby inhibiting the ability of DNA repair.
脱氧雪腐镰刀菌烯醇(DON)是最常见的霉菌毒素之一。本研究旨在使用多种细胞和分子检测方法评估细胞毒性、遗传毒性以及氧化损伤,并探讨其在人外周血淋巴细胞中的机制。将人外周血淋巴细胞在 DON 的 8 个不同剂量(0、6.25、12.5、25、50、100、250 和 500ng/mL)下培养 6、12 和 24 小时。DON 能够降低细胞活力,并在培养的所有时间内对细胞膜、染色体或 DNA 造成损伤。它还能够在 6、12 和 24 小时诱导脂质过氧化,增加 8-OHdG 和 ROS 的水平。RT-PCR 和 Western Blot 的结果表明,DON 能够在 6 小时增强 DNA 修复基因和 HO-1 的 mRNA 或蛋白表达,并在 24 小时抑制这些表达。DON 可能会引发人外周血淋巴细胞的遗传毒性。这种机制可能与抗氧化酶的耗竭和 DNA 的氧化损伤有关,后者降低了 HO-1 的表达,从而抑制了 DNA 修复的能力。