Comparative hepatotoxicity of deoxynivalenol in rat, mouse and human liver cells in culture.
The present study was undertaken to assess, in vitro, the hepatotoxic potential of the food-borne mycotoxin, deoxynivalenol (DON), using rat (Clone9 and MH1C1), mouse (NBL CL2) and human (WRL68 and HepG2) liver cells in culture. The cells were treated with DON for 24 h at 37 degrees C in 5% CO(2) at concentrations of 0-25 microg ml(-1). Following the treatment period, the cells were assayed for biochemical markers of hepatotoxicity that included three independent cytotoxicity assays, oxidative stress and mitochondrial dysfunction. Concentration-dependent cytotoxicity of DON was observed in each of the five different liver cells derived from three different species (rat, mouse and human) over the entire concentration range studied, beginning at 0.1 microg ml(-1). At these concentrations DON did not induce a biologically significant increase in oxidative stress in these liver cells, and showed a significant decrease in the mitochondrial function only in the rat liver MH1C1 cells compared with the control. The results of this in vitro study suggest that DON is a potential hepatotoxin for the rat, mouse and human liver cells in the concentration range tested in this study. The liver cells used in this study showed distinct endpoint-sensitivity to DON related to the species.
Sahu
Saura C
SC
Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708, USA. saura.sahu@fda.hhs.gov
O'Donnell
Michael W
MW
Wiesenfeld
Paddy L
PL
D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D005517:Foodborne Diseases / Q000209:etiology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D013045:Species Specificity; D014255:Trichothecenes / Q000633:toxicity*
D014255:Trichothecenes; C007262:deoxynivalenol