Comparative study of the toxic effects of fumonisin B1 in rat C6 glioma cells and p53-null mouse embryo fibroblasts.
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.
Mobio
Théophile A
TA
Laboratory of Toxicology, University Victor Segalen Bordeaux 2, 146 rue Léo-Saignat, 33076 Bordeaux, France.
Tavan
Emmanuelle
E
Baudrimont
Isabelle
I
Anane
Rachid
R
Carratú
Maria Rosaria
MR
Sanni
Ambaliou
A
Gbeassor
Messanvi F
MF
Shier
Thomas W
TW
Narbonne
Jean-François
JF
Creppy
Edmond E
EE
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*
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