title: Comparative study of the toxic effects of fumonisin B1 in rat C6 glioma cells and p53-null mouse embryo fibroblasts.
abstract: The present experiments have been carried out in order to study (comparatively) oxidative stress and its consequences (i.e. modifications of DNA bases and/or DNA fragmentation), cell cycle progression (through two generations) and apoptosis in C6 glioma cells (with normal p53 status) and p53-null mouse embryonic fibroblasts (MEF) after incubation with fumonisin B(1) (FB(1)). Further endpoints, including protein and DNA syntheses as well as cytotoxicity, have been also studied. The results show that FB(1) (incubation) produced a significant increase of malondialdehyde (MDA) production (suggestive of lipid peroxidation) which was prevented by antioxidant agents in both cell types. Moreover, FB(1) induced a significant and dose-related increase of 8-OH-dG and DNA fragmentation in both C6 glioma and MEF cells. Unlike MEF cells, apoptotic C6 glioma cells were observed after FB(1) incubation. Moreover, suppression of cell cycle progression was observed in C6 glioma but not in MEF cell incubated with FB(1). The results suggest a possible loss of protective mechanisms (such as p53-dependent apoptosis and cell cycle arrest) in FB(1)-damaged MEF cells and confirm that cells lacking of mechanisms governed by p53 gene would be more susceptible to neoplastic cascade or mutation following DNA lesions induced by this mycotoxin.
authors.affiliation: Laboratory of Toxicology, University Victor Segalen Bordeaux 2, 146 rue Léo-Saignat, 33076 Bordeaux, France.
authors.forename: Théophile A
authors.initials: TA
authors.lastname: Mobio
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Tavan
authors.forename: Isabelle
authors.initials: I
authors.lastname: Baudrimont
authors.forename: Rachid
authors.initials: R
authors.lastname: Anane
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Carratú
authors.forename: Ambaliou
authors.initials: A
authors.lastname: Sanni
authors.forename: Messanvi F
authors.initials: MF
authors.lastname: Gbeassor
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Shier
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Narbonne
authors.forename: Edmond E
authors.initials: EE
authors.lastname: Creppy
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D020552:Comet Assay; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D037341:Fumonisins / Q000633:toxicity*; D005910:Glioma / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
chemical_list: C065701:5-methyldeoxycytosine; D002274:Carcinogens, Environmental; D037341:Fumonisins; D017392:Thiobarbituric Acid Reactive Substances; D016159:Tumor Suppressor Protein p53; C056933:fumonisin B1; D008315:Malondialdehyde; D044503:5-Methylcytosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003596:Cytosine; D004247:DNA; D003849:Deoxyguanosine