Killilea David W, Chow Darryl, Xiao Sheng Qi, Li Charles, Stoller Marshall L
Children's Hospital Oakland Research Institute, Oakland, CA, USA.
Department of Urology, University of California, San Francisco, CA, USA.
Toxicol Rep. 2017 May 17;4:260-264. doi: 10.1016/j.toxrep.2017.05.003. eCollection 2017.
Prolonged exposure to the flame retardants found in many household products and building materials is associated with adverse developmental, reproductive, and carcinogenic consequences. While these compounds have been studied in numerous epidemiological and animal models, less is known about the effects of flame retardant exposure on cell function. This study evaluated the toxicity of the commonly used fire retardant tris(1,3-dichloro-2-propyl)phosphate (TDCPP) in cell line derived from the kidney, a major tissue target of organohalogen toxicity. TDCPP inhibited cell growth at lower concentrations (IC 27 μM), while cell viability and toxicity were affected at higher concentrations (IC 171 μM and 168 μM, respectively). TDCPP inhibited protein synthesis and caused cell cycle arrest, but only at higher concentrations. Additionally, the antioxidant -acetylcysteine (NAC) reduced cell toxicity in cells treated with TDCPP, suggesting that exposure to TDCPP increased oxidative stress in the cells. In summary, these data show that low concentrations of TDCPP result in cytostasis in a kidney cell line, whereas higher concentrations induce cell toxicity. Furthermore, TDCPP toxicity can be attenuated by NAC, suggesting that antioxidants may be effective countermeasures to some organohalogen exposures.
长期接触许多家用产品和建筑材料中含有的阻燃剂会导致不良的发育、生殖和致癌后果。虽然这些化合物已在众多流行病学和动物模型中得到研究,但关于阻燃剂暴露对细胞功能的影响却知之甚少。本研究评估了常用阻燃剂磷酸三(1,3 - 二氯 - 2 - 丙基)酯(TDCPP)对源自肾脏的细胞系的毒性,肾脏是有机卤素毒性的主要组织靶点。TDCPP在较低浓度(IC₂₇ μM)时抑制细胞生长,而在较高浓度(分别为IC₁₇₁ μM和168 μM)时影响细胞活力和毒性。TDCPP抑制蛋白质合成并导致细胞周期停滞,但仅在较高浓度时才会出现。此外,抗氧化剂N - 乙酰半胱氨酸(NAC)降低了用TDCPP处理的细胞的毒性,这表明暴露于TDCPP会增加细胞内的氧化应激。总之,这些数据表明低浓度的TDCPP会导致肾脏细胞系细胞生长停滞,而高浓度则会诱导细胞毒性。此外,NAC可减轻TDCPP的毒性,这表明抗氧化剂可能是应对某些有机卤素暴露的有效对策。