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  • Title: [The effect of dibutyl phthalate (DBP) on the methylation and expression level of p53 gene in the liver of Wistar rats].
    Author: Urbanek-Olejnik K, Liszewska M, Kostka G.
    Journal: Rocz Panstw Zakl Hig; 2012; 63(4):425-32. PubMed ID: 23631263.
    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. MATERIAL AND METHOD: 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.
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