Transcriptome profiling of HepG2 cells exposed to the flame retardant 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO)

Boris V. Krivoshiev, Gerrit T. S. Beemster, Katrien Sprangers, Bart Cuypers, Kris Laukens, Ronny Blust, Steven J. Husson

Research output: Contribution to journalA1: Web of Science-article

Abstract

The flame retardant, 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO), has been receiving great interest given its superior fire protection properties, and its predicted low level of persistence, bioaccumulation, and toxicity. However, empirical toxicological data that are essential for a complete hazard assessment are severely lacking. In this study, we attempted to identify the potential toxicological modes of action by transcriptome (RNA-seq) profiling of the human liver hepatocellular carcinoma cell line, HepG2. Such insight may help in identifying compounds of concern and potential toxicological phenotypes. DOPO was found to have little cytotoxic potential, with lower effective concentrations compared to other flame retardants studied in the same cell line. Differentially expressed genes revealed a wide range of molecular effects including changes in protein, energy, DNA, and lipid metabolism, along with changes in cellular stress response pathways. In response to 250 mu M DOPO, the most perturbed biological processes were fatty acid metabolism, androgen metabolism, glucose transport, and renal function and development, which is in agreement with other studies that observed similar effects of other flame retardants in other species. However, treatment with 2.5 mu M DOPO resulted in very few differentially expressed genes and failed to indicate any potential effects on biology, despite such concentrations likely being orders of magnitude greater than would be encountered in the environment. This, together with the low levels of cytotoxicity, supports the potential replacement of the current flame retardants by DOPO, although further studies are needed to establish the nephrotoxicity and endocrine disruption of DOPO.

Original languageEnglish
JournalToxicology Research
Volume7
Issue number3
Pages (from-to)492-502
Number of pages11
ISSN2045-452X
DOIs
Publication statusPublished - 2018

Keywords

  • POLYBROMINATED DIPHENYL ETHERS
  • TRIS 2-BUTOXYETHYL PHOSPHATE
  • MESSENGER-RNA EXPRESSION
  • IN-VITRO NEUROTOXICITY
  • THYROID-HORMONE LEVELS
  • OXIDATIVE STRESS
  • DAPHNIA-MAGNA
  • HEXABROMOCYCLODODECANE HBCD
  • DEVELOPMENTAL TOXICITY
  • TRIPHENYL PHOSPHATE

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