DNA damage and methylation induced by organophosphate flame retardants: Tris(2-chloroethyl) phosphate and tris(1-chloro-2-propyl) phosphate in human peripheral blood mononuclear cells

Hum Exp Toxicol. 2019 Jun;38(6):724-733. doi: 10.1177/0960327119839174. Epub 2019 Apr 1.

Abstract

Phosphorus flame retardants are a group of chemicals that are used to slow or prevent the spread of fire. These compounds have been detected in different environments including human organism. In the present study, we have investigated DNA-damaging potential and effect on DNA methylation of tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propyl) phosphate (TCPP) in human peripheral blood mononuclear cells (PBMCs). In order to determine DNA damage and repair, the alkaline and neutral versions of the comet assay were used. The level of DNA methylation was determined with specific antibodies against methylated DNA. PBMCs were exposed to TCEP and TCPP at the concentrations in the range of 1-1000 µM for 24 h. We have observed that TCEP and TCPP induced DNA damage-DNA breaks and alkali-labile sites. All DNA damages were effectively repaired during 120-min repair incubation. The results have also shown that TCEP and TCPP decreased the level of DNA methylation in PBMCs. In the case of TCEP, this effect was observed at a very low concentration of 1 µM.

Keywords: DNA damage; DNA methylation; DNA repair; flame retardants.

MeSH terms

  • Adolescent
  • Adult
  • Cells, Cultured
  • DNA Damage*
  • DNA Methylation*
  • Flame Retardants / toxicity*
  • Humans
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Middle Aged
  • Organophosphates / toxicity*
  • Organophosphorus Compounds / toxicity*
  • Young Adult

Substances

  • Flame Retardants
  • Organophosphates
  • Organophosphorus Compounds
  • tri-(2-chloroisopropyl)phosphate
  • tris(chloroethyl)phosphate