Tris (1,3-dichloro-2-propyl) phosphate treatment induces DNA damage, cell cycle arrest and apoptosis in murine RAW264.7 macrophages.
Tris (1,3-dichloro-2-propyl) phosphate treatment induces DNA damage, cell cycle arrest and apoptosis in murine RAW264.7 macrophages.
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DOI：
10.2131/jts.44.134
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发表时间：
2019
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影响因子：
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通讯作者：
Wei Zhang;Ruiguo Wang;J. Giesy;Yang-Bo Li;Peilong Wang
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文献类型：
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作者：
Wei Zhang;Ruiguo Wang;J. Giesy;Yang-Bo Li;Peilong Wang
三（1,3-二氯-2-丙基）磷酸（TDCPP）是目前使用最广泛的有机磷阻燃剂，目前已取代多溴二苯醚（PBDEs）使用。TDCPP在土壤、水、空气和生物群等无机环境基质中经常被检测到。TDCPP对细胞的体外作用此前尚未得到阐明。因此，本研究在RAW264.7巨噬细胞中研究TDCPP对细胞毒性、DNA损伤、细胞周期分布、细胞凋亡的影响。TDCPP以浓度依赖的方式降低RAW264.7细胞的活力，并通过彗星试验检测到DNA损伤，并导致γ-H2AX水平上调。与对照组相比，TDCPP在12小时时使RAW264.7细胞内的活性氧（ROS）水平增加了1.44倍。暴露于TDCPP的细胞中，处于细胞周期G1期和G2期的细胞百分比呈剂量依赖性增加。TDCPP显著下调细胞周期G1、G2期调控因子CDK-4、Cyclin D1、Cyclin B1、CDC-2的表达。这些结果表明，TDCPP具有细胞毒性，可损伤RAW264.7细胞的DNA，导致细胞周期阻滞在G1和G2期，导致细胞凋亡，提示有必要在细胞水平上评估TDCPP对免疫系统的影响。
Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) is the most widely used organophosphorus flame retardant, which is now used instead of polybrominated diphenyl ethers (PBDEs). TDCPP has frequently been detected in inorganic environmental matrices, such as soil, water and air as well as biota. In vitro effects of TDCPP on cells had not been previously elucidated. Therefore, in the present study, cytotoxicity, DNA damage, cell cycle distribution, apoptosis caused by TDCPP was studied in RAW264.7 macrophage cells. TDCPP reduced viability of RAW264.7 cells in a concentration-dependent manner and caused damage to DNA that was detected by use of the comet assay and caused up-regulation of the level of γ-H2AX. TDCPP increased the intracellular reactive oxygen species (ROS) level in RAW264.7 cells up to 1.44-fold compared to the control group at 12 hr. Percentages of cells in G1 and G2 phases of the cell cycle were dose-dependently greater in cells exposed to TDCPP. TDCPP significantly down-regulated expression of CDK-4, Cyclin D1, Cyclin B1, CDC-2, which are regulators of G1 and G2 phases of the cell cycle. These results demonstrated that TDCPP is cytotoxic and damages DNA in RAW264.7 cells, which resulted in arrest of the cell cycle at G1 and G2 phases and resulted in apoptosis, suggest the necessity to evaluate the effects of TDCPP on the immune system at the cellular level.