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 B₁ (FB₁). Further endpoints, including protein and DNA syntheses as well as cytotoxicity, have been also studied. The results show that FB₁ (incubation) produced a significant increase of malondialdehyde (MDA) production (suggestive of lipid peroxidation) which was prevented by antioxidant agents in both cell types. Moreover, FB₁ 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 FB₁ incubation. Moreover, suppression of cell cycle progression was observed in C6 glioma but not in MEF cell incubated with FB₁. The results suggest a possible loss of protective mechanisms (such as p53-dependent apoptosis and cell cycle arrest) in FB₁-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.