Fumonisin B1-induced toxicity and oxidative damage in U-118MG glioblastoma cells.
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.
Stockmann-Juvala
Helene
H
Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, 00250 Helsinki, Finland. helene.stockmann@ttl.fi
Mikkola
Jouni
J
Naarala
Jonne
J
Loikkanen
Jarkko
J
Elovaara
Eivor
E
Savolainen
Kai
K
D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D037341:Fumonisins / Q000633:toxicity*; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009183:Mycotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D037341:Fumonisins; D009183:Mycotoxins; D017382:Reactive Oxygen Species; C056933:fumonisin B1; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione