Toxicological effects of tris(2-chloropropyl) phosphate in human hepatic cells

Chemosphere. 2017 Nov:187:88-96. doi: 10.1016/j.chemosphere.2017.08.083. Epub 2017 Aug 22.

Abstract

Organophosphate flame retardants (OPFRs) are widely used as flame retardants which are ubiquitous in various environment media. As many of OPFRs are toxic and persistent, concerns have been raised in regards to their environmental impact. In this study, the toxicological effects of tris(2-chloropropyl) phosphate (TCPP) in human L02 cells was investigated by cell proliferation and apoptosis, oxidative stress, metabolomic and proteomic responses as well as gene expressions related to apoptosis. Results showed that TCPP did not significantly affect the L02 cell apoptosis, however, a significant increase of ROS production was observed in L02 cells with TCPP treatment compared with that in control group (p < 0.05). The expression levels of Bcl-2 family-encoding genes (Bax, Hrk and Bax/Bcl-2) were up-regulated significantly in 10-4 M group (p < 0.05). Metabolomic and proteomic responses indicated that TCPP mainly caused disturbance in cell growth/division and gene expression, energy and material metabolism, signal transduction, defense and cytoskeleton, which was further confirmed by the western blot analysis.

Keywords: Cell apoptosis; L02 cells; Metabolomics; Proteomics; ROS; Tris(2-chloropropyl) phosphate (TCPP).

MeSH terms

  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Flame Retardants / analysis
  • Flame Retardants / toxicity*
  • Gene Expression Regulation / drug effects*
  • Hepatocytes / drug effects*
  • Hepatocytes / pathology
  • Humans
  • Liver / chemistry
  • Liver / drug effects
  • Metabolomics
  • Organophosphates / toxicity*
  • Oxidative Stress / drug effects
  • Proteomics / methods*

Substances

  • Flame Retardants
  • Organophosphates