RNA-Seq shows pollutant TDCP causes hepatotoxicity and inflammation in fish

Chemical Watch – A team of Chinese, Singaporean and North American researchers have shown how the flame retardant tris(1,3-dichloro-2-propyl) phosphate (TDCP) affects fish livers.

TDCP is widely used in plastics, textiles, varnishes, electronics equipment and furniture. It is often used as a replacement for polybrominated diphenyl ether (PBDE) retardants but its use in toys is restricted by the EU (CW 20 June 2014). It is classified under the CLP Regulation as a category 2 carcinogen.

It is also known to be a contaminant in indoor air, household dust, rivers (CW 28 May 2013), wildlife and human tissue.

In a paper published in Nature, the researchers say they investigated the toxicity of TDCP to the liver, using zebra fish exposed to three different levels of the substance. The fish livers were analysed through RNA-Sequencing (RNA-Seq) and reverse transcription quantitative polymerase chain reaction (RT-qPCR) to understand the molecular mechanisms of toxicity.

rna-seq

Dose- (A) and time-dependent (B) effects on the expression of selected hepatotoxicity biomarker genes (gclc, gsr and nqo1) in response to TDCIPP.(C): control group; T: treatment group. Values represent mean ± SEM (n = 9). Asterisks indicate significant differences from matched control samples (P < 0.05).

The results identified 583 differentially expressed genes (306 up-regulated and 277 down-regulated) in exposed fish compared with controls. Up-regulated genes included those involved in stress, immune and inflammatory responses. Hepatic inflammation was further confirmed by microscopic cell observations.

The up- and down-regulated genes were subjected to Gene Ontology (GO) enrichment and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses – methods involving databases of known metabolism, genetics and cell signalling pathways.

The exposure to TDCP significantly up-regulated the expression of several biomarker genes for hepatotoxicity, caused hepatic vacuolisation and apoptosis of liver cells, and an increase in liver size.

Liu C, Su G, Giesy JP, Letcher RJ, Li G, Agrawal I, Li J, Yu L, Wang J, Gong Z. (2016) Acute Exposure to Tris(1,3-dichloro-2-propyl) Phosphate (TDCIPP) Causes Hepatic Inflammation and Leads to Hepatotoxicity in Zebrafish. Sci Rep 6:19045. [article]

SourceChemical Watch by Philip Lightowlers

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