The cytotoxicity of organophosphate flame retardants on HepG2, A549 and Caco-2 cells

Abstract

In order to elucidate the cytotoxicity of organophosphate flame retardants (OPFRs), three human in vitro models, namely the HepG2 hepatoma cells, the A549 lung cancer cells and the Caco-2 colon cancer cells, were chosen to investigate the toxicity of triphenyl phosphate (TPP), tributylphosphate (TBP), tris(2-butoxyexthyl) phosphate (TBEP) and tris (2-chloroisopropyl) phosphate (TCPP). Cytotoxicity was assayed in terms of cell viability, DNA damage status, reactive oxygen species (ROS) level and lactate dehydrogenase (LDH) leakage. The results showed that all these four OPFRs could inhibit cell viability, overproduce ROS level, induce DNA lesions and increase the LDH leakage. In addition, the toxic effects of OPFRs in Caco-2 cells were relatively severer than those in HepG2 and A549 cells, which might result from some possible mechanisms apart from oxidative stress pathway. In conclusion, TBP, TPP, TBEP and TCPP could induce cell toxicity in various cell lines at relatively high concentrations as evidenced by suppression of cell viability, overproduction of ROS, induction of DNA lesions and increase of LDH leakage. Different cell types seemed to have different sensitivities and responses to OPFRs exposure, as well as the underlying potential molecular mechanisms.

Tris (1,3-dichloro-2-propyl) phosphate treatment induces DNA damage, cell cycle arrest and apoptosis in murine RAW264.7 macrophages

“…Specifically, TDCPP caused DNA double-strand breaks and up-regulated expression of γ-H2AX. Results of previous studies have demonstrated that some OPFRs, such as TCEP and, tris (2-chloroisopropyl) phosphate (TCPP) also damage DNA (An et al, 2016). Alternatively, TCPP did not break DNA of V79 cells or in eight strains of the bacterium Salmonella, which indicated the different effect between compounds and cell models used (Föllmann and Wober, 2006).…”

“…Alternatively, TCPP did not break DNA of V79 cells or in eight strains of the bacterium Salmonella, which indicated the different effect between compounds and cell models used (Föllmann and Wober, 2006). ROS can function as "redox messengers" in intracellular signaling (Yang et al, 2014) and inducers of oxidative damage, which are related to various biological processes, such as DNA damage, viability, proliferation and death of cells (An et al, 2016). Our results showed that the RAW264.7 cells began to produce ROS when the exposure time reached 6 hr, the increasing rate peaked at 12 hr.…”

“…The results suggested that cytotoxicity and DNA damage induced by TDCPP might result from the high level of ROS caused by TDCPP. ROS also played an important role in cytotoxicity induced by TCPP and tris(2-butoxyexthyl) phosphate (TBEP) on HepG2 and A549 cells, but not on Caco-2 cells (An et al, 2016).…”

Tributylphosphate (TBP) and tris (2-butoxyethyl) phosphate (TBEP) induced apoptosis and cell cycle arrest in HepG2 cells

“…39 Our previous study also showed that TBP and TBEP exposure (24 h) below 100 μM seems to have no remarkable proliferation-inhibiting effect on HepG2, human lung cancer (A549) and human colon cancer (Caco-2) cells. 40 Reactive oxygen species (ROS) are well-established inducers of oxidative damage, which is closely related to cell viability, proliferation and cell death. 41 ROS formation might be a pivotal mechanism behind the toxicity of multiple environmental chemical toxins, such as polychlorinated biphenyls (PCBs), PBDEs, organic phosphorus pesticides, etc.…”

A toxicogenomics approach to screen chlorinated flame retardants tris(2‐chloroethyl) phosphate and tris(2‐chloroisopropyl) phosphate for potential health effects

“…Compared to other organophosphate FRs tested within the same cell line, TCEP had some of the lowest levels of cytotoxicity measured. For instance, tributylphosphate, tris(2‐butoxyethyl) phosphate and tris(1‐chloro‐2‐propyl)phosphate showed significant effects on HepG2 cell viability at 200 μ m after 24 hours treatment (An et al, ), while tris(1,3‐dichloro‐2‐propyl) phosphate, a structural analogue of TCIPP, had an IC 50 of 84.0 μ m after 72 hours of exposure (Zhang, Williams, et al, 2016). However, it should be noted that perhaps TCIPP cytotoxic effects only occur at doses higher than 100 μ m , the maximum dose used in this study, as evidenced by cytotoxic effects only being seen at 200 μ m in the same cell line that was used in this study (An et al, ).…”