title: [The effect of dibutyl phthalate (DBP) on the methylation and expression level of p53 gene in the liver of Wistar rats].
abstract: BACKGROUND
  Currently, nongenotoxic carcinogens-induced changes in DNA methylation profile are considered as mechanism of their toxicity, including carcinogenic action.
  
  
  OBJECTIVE
  The aim of the study was to determine the effect of dibutyl phthalate (DBP) on the methylation levels of the p53 promoter region, as well as mRNA and protein level of this gene.
  
  
  METHODS
  Male Wistar rats received DBP in one, three or fourteen daily oral doses (at 24-h intervals) of 1800 mg/kg b.w. x day(-1). The methylation level of c-myc gene was determined by PCR-based methylation sensitive restriction enzyme analysis (MSRA). The expression of gene was assessed by Real-Time PCR (at mRNA level) and Western blot (at protein level) analysis.
  
  
  RESULTS
  There was observed the hypermethylation of p53 promoter region after short (1 day) exposure of the animals to DBP. No correlation was found between mRNA expression and methylation level of p53 gene. The present study showed decreased level of p53 protein, during the whole period of study.
  
  
  CONCLUSIONS
  No direct correlation was observed between the methylation and expression level of p53. The decreased protein level might be a consequence of the repressive effect of c-myc, which was involved in signal transduction pathways, the same as p53 protein.
authors: Zakład Toksykologii i Oceny Ryzyka, Narodowy Instytut Zdrowia Publicznego - Państwowy Zakład Higieny, Warszawa.
authors: Katarzyna
authors: K
authors: Urbanek-Olejnik
authors: Monika
authors: M
authors: Liszewska
authors: Grazyna
authors: G
authors: Kostka
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D003993:Dibutyl Phthalate / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects* / Q000235:genetics*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008745:Methylation; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D036401:Toxicity Tests, Chronic
chemical_list: D002273:Carcinogens; D012333:RNA, Messenger; D003993:Dibutyl Phthalate