Epigenetic properties of fumonisin B1: Cell cycle arrest and DNA base modification in C6 glioma cells

Théophile A. Mobio, Rachid Anane, Isabelle Baudrimont, Maria Rosaria Carratú, W. Thomas Shier, Sébastien D. Dano, Yoshio Ueno, Edmond E. Creppy

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Fumonisin B1 produced by the fungus Fusarium moniliforme is a member of a new class of sphinganine analogue mycotoxins that occur widely in the food chain. Epidemiological studies associate FB1 with human (esophageal cancer in China and South Africa. FB1 also causes acute pulmonary edema in pigs and equine leucoencephalomalacia. This disease is thought to be a consequence of inhibition by FB1 of cellular ceramide synthesis in cells. To investigate further on this pathogenesis, the effect of FB1 was studied on cell viability (3 to 54 μM of FB1), protein (2.5 to 20 μM of FB1) and DNA syntheses (2.5 to 50 μM of FB1), and cellular cycle (3 to 18 μM of FB1) of rat C6 glioma cells after 24 h incubation. The results of the viability test show that FB1 induces 10 ± 2% and 47 ± 4% cell death with, respectively, 3 and 54 μM, in C6 cells. This cytotoxicity induced by FB1 was efficiently prevented when the cells were preincubated 24 h with vitamin E (25 μM). FB1 displays epigenetic properties since it induced hypermethylation of the DNA (9-18 μM). Inhibition of protein synthesis was observed with FB1 with an IC50 of 6 μM showing that C6 glioma cells are very sensitive to FB1; however, the synthesis of DNA was only slightly inhibited, up to 20 μM of FB1. The flow cytometry showed that the number of cells in phase S decreased significantly as compared to the control p = 0.01 from 18.7 ± 2.5% to 8.1 ± 1.1% for 9 μM FB1. The number of cells in phase G2/M increased significantly as compared to the control (p ≤ 0.05) from 45.7 ± 0.4% to 54.8 ± 1.1% for 9 μM FB1, whereas no change occurs in the number of cells in the phase G0/H1. These results show that cytotoxic concentrations of FB1 induce cellular cycle arrest in phase G2/M in rat C6 glioma cells possibly in relation with genotoxic events. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)91-96
Number of pages6
JournalToxicology and Applied Pharmacology
Volume164
Issue number1
DOIs
StatePublished - Apr 1 2000

Keywords

  • C6 glioma cells
  • Cell cycle arrest
  • Fumonisin B1
  • Hypermethylation of the DNA

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