title: Role of fumonisin B1 on DNA methylation changes in rat kidney and liver cells.
abstract: BACKGROUND
  Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides (Sacc.) Nirenberg (Nectriaceae) mold that contaminates maize and other agricultural products. Although the effects of FB1 on sphingolipid metabolism are clear, little is known about early molecular changes associated with FB1 carcinogenicity.
  
  
  OBJECTIVE
  Alteration on DNA methylation, as an early event in non-genotoxic carcinogenesis, may play an important role in the mechanism of FB1 toxiciy.
  
  
  METHODS
  Dose-related effects of FB1 (1-50 µM for 24 h) on global DNA methylation by using high-performance liquid chromatography with UV-diode array detection (HPLC-UV/DAD) and CpG promoter methylation by methylation-specific PCR (MSP) were performed in rat liver (Clone 9) and rat kidney (NRK-52E) epithelial cells.
  
  
  RESULTS
  Cell viability reduction is 39% and 34% by the XTT test and LDH release in the growth medium is 32% and 26% at 200 µM of FB1 treatment in Clone 9 and NRK-52E cells, respectively. No significant dose-related effects of FB1 on global DNA methylation which ranged from 4 to 5% were observed in both cells compared with controls. Promoter regions of c-myc gene were methylated (>33%) at 10 and 50 µM of FB1 treatment in Clone 9 cells while it was unmethylated in NRK-52E cells. Promoter regions of p15 gene were unmethylated while VHL gene were found to be methylated (>33%) at 10, 25, and 50 µM and 10 and 50 µM of FB1 treatment in Clone 9 and NRK-52E cells, respectively.
  
  
  CONCLUSIONS
  Alteration in DNA methylation might play an important role in the toxicity of FB1 in risk assessment process.
authors: Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University , Beyazit, Istanbul , Turkey.
authors: Goksun
authors: G
authors: Demirel
authors: Buket
authors: B
authors: Alpertunga
authors: Sibel
authors: S
authors: Ozden
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D018899:CpG Islands; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects*; D037341:Fumonisins / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D016259:Genes, myc; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D051381:Rats; D018570:Risk Assessment; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
chemical_list: D015820:Cadherins; C493969:Cdkn2b protein, rat; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D037341:Fumonisins; C056933:fumonisin B1; D051794:Von Hippel-Lindau Tumor Suppressor Protein
keywords: Clone 9 cells; NRK-52E cells; cytotoxicity