title: Rat liver clone-9 cells in culture as a model for screening hepatotoxic potential of food-related products: hepatotoxicity of deoxynivalenol.
abstract: Deoxynivalenol (DON) is a mycotoxin food contaminant found in several cereal grains. The literature on the liver toxicity of DON in vivo is conflicting and does not clearly characterize its hepatotoxic effects. Cultured rat liver clone-9 cells were used as a model to assess the hepatotoxic potential of DON. The cell cultures, seeded onto 96-well plates, were treated at confluence with varying concentrations of DON (0-100 microg ml(-1)) for 48 h at 37 degrees C in 5% CO2. After the treatment period, the cells were assayed for a number of hepatotoxic endpoints that included cytotoxicity, double-stranded DNA (ds-DNA) content, oxidative stress and mitochondrial function. The concentration-dependent toxicity of DON, as measured by cytotoxicity and ds-DNA content, was observed over the entire concentration range studied beginning at 0.5 microg ml(-1). DON also induced a significant concentration-dependent increase in oxidative stress at DON concentrations starting at 10 microg ml(-1). The mitochondrial function of the treated cells decreased with the increasing concentration of DON exposure, but it was not statistically different from that of the control value. Liver histopathology observed at 3, 24 and 72 h following a single intraperitoneal administration dose of DON (10 mg kg(-1) BW) to adult male rats is consistent with early mild hepatotoxicity. The overall results of this study suggest that acute DON exposure has early mild cytotoxic effects on hepatocytes in vivo that are expressed as severe effects in rat liver clone-9 cells in vitro.
authors.affiliation: Division of Toxicology, Center for Food Safety and Applied Nutrition, U. S. Food and Drug Administration, Laurel, MD 20708, USA. saura.sahu@fda.hhs.gov
authors.forename: Saura C
authors.initials: SC
authors.lastname: Sahu
authors.forename: Larry H
authors.initials: LH
authors.lastname: Garthoff
authors.forename: Martin G
authors.initials: MG
authors.lastname: Robl
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Chirtel
authors.forename: Dennis I
authors.initials: DI
authors.lastname: Ruggles
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Flynn
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sobotka
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D002999:Clone Cells; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005506:Food Contamination; D022781:Hepatocytes / Q000187:drug effects*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014255:Trichothecenes / Q000633:toxicity*
chemical_list: D014255:Trichothecenes; D004247:DNA; C007262:deoxynivalenol