β-Cypermethrin and its metabolite 3-phenoxybenzoic acid induce cytotoxicity and block granulocytic cell differentiation in HL-60 cells  

作　　者：Bingnan He Xia Wang Lai Wei Baida Kong Yuanxiang Jin Xiaoxian Xie Zhengwei Fu 

机构地区：[1]College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China

出　　处：《Acta Biochimica et Biophysica Sinica》2018年第8期740-747,共8页生物化学与生物物理学报（英文版）

摘　　要：The most widely used type Ⅱ pyrethroid is β-cypermethrin （β-CYP）, and 3-phenoxybenzoic acid （3-PBA） is one of its primary metabolites. Although CYP has been shown to pose toxic effects in some immune cells, as of now the immunotoxicity of CYP on immune progenitor cells has not been well studied. In this study, we evaluated the immunotoxicity of β-CYP and 3-PBA on the human promyelocytic leukemia cell line, HL-60. Both β-CYP and 3-PBA reduced cell viability. In addition, both β-CYP and 3-PBA stimulated the intrinsic apoptotic pathway in a dose- and time- dependent manner, while only β-CYP induced ceil cycle arrest in G1 stage. Moreover, exposure to β-CYP and 3-PBA at 100 μM inhibited all-trans retinoic acid （ATRA）-induced mRNA expressions of the granulocytic differentiation-related genes, CD11b and CSF-3R. Furthermore, exposure to β-CYP and 3-PBA resulted in a downregulation of the granulocytic differentiation promoting transcrip- tional factors, PU. 1 and C/EBPε. Furthermore, we found that β-CYP and 3-PBA exposure led to ele- vated levels of cellular reactive oxygen species （ROS）, and that pretreatment with N-acetylcysteine （NAC） blocked the toxic effects caused by β-CYP and 3-PBA. The results obtained in the present study provide evidence showing the immunotoxic effects of β-CYP and 3-PBA on promyelocytic cells as well as its possible underlying mechanism.The most widely used type Ⅱ pyrethroid is β-cypermethrin （β-CYP）, and 3-phenoxybenzoic acid （3-PBA） is one of its primary metabolites. Although CYP has been shown to pose toxic effects in some immune cells, as of now the immunotoxicity of CYP on immune progenitor cells has not been well studied. In this study, we evaluated the immunotoxicity of β-CYP and 3-PBA on the human promyelocytic leukemia cell line, HL-60. Both β-CYP and 3-PBA reduced cell viability. In addition, both β-CYP and 3-PBA stimulated the intrinsic apoptotic pathway in a dose- and time- dependent manner, while only β-CYP induced ceil cycle arrest in G1 stage. Moreover, exposure to β-CYP and 3-PBA at 100 μM inhibited all-trans retinoic acid （ATRA）-induced mRNA expressions of the granulocytic differentiation-related genes, CD11b and CSF-3R. Furthermore, exposure to β-CYP and 3-PBA resulted in a downregulation of the granulocytic differentiation promoting transcrip- tional factors, PU. 1 and C/EBPε. Furthermore, we found that β-CYP and 3-PBA exposure led to ele- vated levels of cellular reactive oxygen species （ROS）, and that pretreatment with N-acetylcysteine （NAC） blocked the toxic effects caused by β-CYP and 3-PBA. The results obtained in the present study provide evidence showing the immunotoxic effects of β-CYP and 3-PBA on promyelocytic cells as well as its possible underlying mechanism.

关 键 词：β-cypermethrin 3-phenoxybenzoic acid promyelocytic cells CYTOTOXICITY differentiation block mechanism 

分 类 号：S481.8[农业科学—农药学] Q255[农业科学—植物保护]