Stockmann-Juvala Helene, Mikkola Jouni, Naarala Jonne, Loikkanen Jarkko, Elovaara Eivor, Savolainen Kai
Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, 00250 Helsinki, Finland.
Toxicology. 2004 Oct 1;202(3):173-83. doi: 10.1016/j.tox.2004.05.002.
The mycotoxin fumonisin B1 (FB1) is produced by Fusarium verticillioides, which commonly infects corn and other agricultural products. Fusarium species are also a frequent finding in moisture-damaged buildings, causing possible human exposure to FB1. FB1 is neurotoxic and carcinogenic in a number of animal species. In this study, we have investigated the effects of FB1 on human U-118MG glioblastoma cells. The production of reactive oxygen species (ROS), lipid peroxidation, intracellular reduced glutathione (GSH) levels, cell viability, caspase-3-like protease activity and DNA fragmentation were studied in cells exposed to 0.01-100 microM FB1 for 0.5-144 h. FB1 increased lipid peroxidation and the production of ROS in U-118MG cells, showing significant effects after culture times from 48 to 144 h at dose levels of 10 or 100 microM FB1. These effects were accompanied by changes in the GSH levels and cell viability, which decreased significantly after incubating the cells for 48-144 h with the toxin. Signs of apoptosis were indicated by increased caspase-3-like protease activity and internucleosomal DNA fragmentation. Thus, oxidative stress and apoptosis may be involved in the neurotoxicity induced by FB1.
霉菌毒素伏马菌素B1(FB1)由轮枝镰孢菌产生,该菌通常感染玉米及其他农产品。镰刀菌属在受潮损坏的建筑物中也很常见,可能导致人类接触FB1。FB1对多种动物具有神经毒性和致癌性。在本研究中,我们调查了FB1对人U-118MG胶质母细胞瘤细胞的影响。研究了暴露于0.01 - 100微摩尔FB1 0.5 - 144小时的细胞中活性氧(ROS)的产生、脂质过氧化、细胞内还原型谷胱甘肽(GSH)水平、细胞活力、半胱天冬酶-3样蛋白酶活性和DNA片段化情况。FB1增加了U-118MG细胞中的脂质过氧化和ROS的产生,在10或100微摩尔FB1剂量水平下培养48至144小时后显示出显著影响。这些影响伴随着GSH水平和细胞活力的变化,在用毒素处理细胞48 - 144小时后,GSH水平和细胞活力显著下降。半胱天冬酶-3样蛋白酶活性增加和核小体间DNA片段化表明细胞出现凋亡迹象。因此,氧化应激和凋亡可能参与了FB1诱导的神经毒性。