Wide-ranging genomic effects of plasticisers and related compounds

Curr Drug Metab. 2008 May;9(4):285-303. doi: 10.2174/138920008784220655.

Abstract

The effects of four compounds, bis(2-ethylhexyl)phthalate (BEHP); diisodecylphthalate (DIP); 4-n-octylphenol (OP); 4-chloro-3-methylphenol (CMP), on gene expression (steady-state mRNA levels) across the whole human genome were studied in human TE671 cells. Effects were studied using the Affymetrics GeneChip Human Genome U133 Plus 2.0, HG-U133 Plus 2.0 arrays, The array analyses the expression of 47,000 transcripts and variants, including approximately 38,500 well characterised. All four compounds exerted statistically significant actions, affecting between 4 and 6.5% of all genes. Each compound had its own expression signature. In most instances where there was an effect, steady-state mRNA levels were decreased, although not always. CMP treatment caused most increases in mRNA levels. A mixture of DIP and CMP caused fewer changes in mRNA levels than either of the individual compounds.

Conclusions: These plasticisers affected the steady-state mRNA levels of many human genes. Exposure to these compounds over many years has the potential to influence human health.

MeSH terms

  • Biotinylation
  • Cell Line, Tumor
  • Cluster Analysis
  • DNA / biosynthesis
  • DNA / genetics
  • DNA Primers / pharmacology
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Deoxyribonuclease I / biosynthesis
  • Deoxyribonuclease I / genetics
  • Environmental Pollutants / toxicity*
  • Genomics*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Plasticizers / toxicity*
  • Poly A / genetics
  • RNA, Complementary / biosynthesis
  • RNA, Complementary / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic / drug effects

Substances

  • DNA Primers
  • DNA, Complementary
  • Environmental Pollutants
  • Plasticizers
  • RNA, Complementary
  • RNA, Messenger
  • Poly A
  • DNA
  • Deoxyribonuclease I