Tris(1,3-dichloro-2-propyl) phosphate disrupts cellular metabolism within human embryonic kidney (HEK293) cells

Journal of hazardous materials · 8 authors, 3 centres

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TL;DR

This laboratory study exposed human embryonic kidney (HEK293) cells to the flame retardant TDCIPP.

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The study investigated the effects of TDCIPP, an organophosphate flame retardant, on human embryonic kidney (HEK293) cells. Contrary to prior studies in other human cell lines, TDCIPP at concentrations <1 μM increased HEK293 cell viability rather than causing cytotoxicity. Using Seahorse XF analysis, the study found TDCIPP did not affect mitochondrial respiration but increased the rate of glycolysis, a metabolic pattern known as the Warburg effect, which was linked to decreased intracellular ROS and increased carnosine levels.

STUDY TYPE

other

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preclinical research

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10923128

Tris(1,3-dichloro-2-propyl) phosphate disrupts cellular metabolism within human embryonic kidney (HEK293) cells

Journal of hazardous materials

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ABSTRACT

Abstract Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a widely used, additive flame retardant that migrates from end-use products, leading to ubiquitous exposure of humans around the world. However, little is known about whether TDCIPP disrupts the physiology of human embryonic cells. Therefore, the objective of this study was to determine whether TDCIPP alters cell viability, cellular metabolism, cytosine methylation, and reactive oxygen species (ROS) levels within human embryonic kidney (HEK293) cells. Relative to vehicle controls, TDCIPP (0.015–0.1225 μM) resulted in a concentration-dependent increase in cell viability, a finding that was driven by an increase in relative ATP abundance. Interestingly, TDCIPP (0.061–0.98 μM) increased the rate of glycolysis – an adaptive mechanism consistent with the Warburg effect exhibited by tumorigenic cells. Moreover, relative to vehicle-treated cells, TDCIPP (0.245–15.63 μM) exposure for 48 h (but not 24 h) resulted in a significant, concentration-dependent decrease in ROS in situ, and TDCIPP (0.245 μM) exposure significantly increased carnosine within the histidine metabolism pathway. However, TDCIPP did not affect global 5-methylcytosine (5-mC) methylation (0.015–15.63 μM), cell membrane integrity (0.061–0.98 μM), nor the abundance of mitochondria (0.061–1.95 μM). Overall, our findings with TDCIPP point to a novel mechanism of action that may be relevant to human embryonic stem cells. Keywords: TDCIPP, HEK293 cells, Metabolism, ATP, Warburg effect, Reactive oxygen species

CITATION EXPORT

Sarah Avila-Barnard, Megan Ha, Charvita Nemarugommula et al.. Tris(1,3-dichloro-2-propyl) phosphate disrupts cellular metabolism within human embryonic kidney (HEK293) cells. Journal of hazardous materials. (2024). https://doi.org/10.1016/j.jhazmat.2024.133660

AUTHORS

8 · 3 CENTRES

Sarah Avila-Barnard, Megan Ha, Charvita Nemarugommula, Jenna L Wiegand, Haiyan Ke, Amancio De Souza, Rachel Behar, David C Volz

a Department of Environmental Sciences, University of California, Riverside, CA 92521, USA
b Metabolomics Core Facility, Institute for Integrative Genome Biology, University of California, Riverside, CA, USA
c Stem Cell Core Facility, University of California, Riverside, CA, USA