An Jing, Hu Jingwen, Shang Yu, Zhong Yufang, Zhang Xinyu, Yu Zhiqiang
a Institute of Environmental Pollution and Health, School of Environmental and Chemical Engineering, Shanghai University , Shanghai , China.
b State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences , Guangzhou , China.
J Environ Sci Health A Tox Hazard Subst Environ Eng. 2016 Sep 18;51(11):980-8. doi: 10.1080/10934529.2016.1191819. Epub 2016 Jun 23.
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.
为了阐明有机磷酸酯类阻燃剂(OPFRs)的细胞毒性,选择了三种人类体外模型,即HepG2肝癌细胞、A549肺癌细胞和Caco-2结肠癌细胞,来研究磷酸三苯酯(TPP)、磷酸三丁酯(TBP)、磷酸三(2-丁氧基乙基)酯(TBEP)和磷酸三(2-氯异丙基)酯(TCPP)的毒性。通过细胞活力、DNA损伤状态、活性氧(ROS)水平和乳酸脱氢酶(LDH)泄漏来检测细胞毒性。结果表明,这四种OPFRs均能抑制细胞活力、过量产生ROS水平、诱导DNA损伤并增加LDH泄漏。此外,OPFRs对Caco-2细胞的毒性作用比对HepG2和A549细胞的毒性作用相对更严重,这可能是由氧化应激途径之外的一些可能机制导致的。总之,TBP、TPP、TBEP和TCPP在相对较高浓度下可诱导各种细胞系产生细胞毒性,表现为细胞活力受抑制、ROS过量产生、DNA损伤诱导以及LDH泄漏增加。不同细胞类型对OPFRs暴露似乎具有不同的敏感性和反应,以及潜在的分子机制。