DNA methylation of estrogen receptor alpha gene by phthalates

J Toxicol Environ Health A. 2005 Dec 10;68(23-24):1995-2003. doi: 10.1080/15287390491008913.


The phthalates are ubiquitous industrial plasticizers and include agents such as di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and butyl benzyl phthalate (BBP), which are classified as endocrine disruptors because of their anti-androgenic or pro-estrogenic effects. A recent study suggested that DBP produced the hypomethylation of c-myc protooncogene in mouse liver to activate c-myc. In the present study, DNA hypomethylation at the promoter region of the estrogen receptor alpha (ERalpha) gene was investigated by methylation-specific polymerase chain reaction (MSP) in a human breast cancer (MCF7) and in a normal (MCF10A) cell line after DBP treatment. Yeast-based estrogen receptor transcription assays showed that hERalpha gene expression was induced by BBP but not DBP. Moreover, MCF7 cells treated with BBP or DBP at 10(-5)M led to the demethylation of ERalpha promoter-associated CpG islands. These data suggest that an altered ER mRNA expression by BBP might be related to aberrant DNA methylation in the promoter region of ERalpha.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • CpG Islands
  • DNA Methylation*
  • DNA, Complementary / metabolism
  • Dibutyl Phthalate / toxicity
  • Diethylhexyl Phthalate / toxicity
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Gene Expression Regulation / drug effects
  • Humans
  • Phthalic Acids / toxicity*
  • Plasticizers / toxicity*
  • Saccharomyces cerevisiae / metabolism
  • beta-Galactosidase / metabolism


  • DNA, Complementary
  • Estrogen Receptor alpha
  • Phthalic Acids
  • Plasticizers
  • Dibutyl Phthalate
  • Diethylhexyl Phthalate
  • beta-Galactosidase
  • butylbenzyl phthalate