Liu Qiaoyun, Wang Longsheng, Chen Hanwen, Huang Bo, Xu Jiawei, Li Ying, Héroux Paul, Zhu Xinqiang, Wu Yihua, Xia Dajing
Department of Toxicology of School of Public Health , and Department of Gynecologic Oncology of Women's Hospital , Zhejiang University School of Medicine , China . Email:
Department of Nutrition of School of Public Health , Zhejiang University School of Medicine , China.
Toxicol Res (Camb). 2019 Jul 26;8(6):833-841. doi: 10.1039/c9tx00080a. eCollection 2019 Nov 1.
Prometryn is a slightly to moderately toxic herbicide belonging to the triazine family of herbicides, which are widely used in agriculture to control the growth of various weeds. Although many studies have shown that triazine herbicides have carcinogenic potential in humans, the cytotoxic effects of prometryn on human cells, and the mechanisms underlying these effects, are not yet fully understood. The lung is one of the most important organs where there is accumulation of environmental pollutants. The aim of this study was to determine the cytotoxic effects of prometryn on normal lung cells using the human bronchial epithelial cell line BEAS-2B. We found that treatment with high concentrations of prometryn arrested BEAS-2B cell growth in the S phase, while at low concentrations the cell cycle was not affected. Furthermore, we observed changes in the expression levels of cyclin-dependent kinase 2 (CDK2) and cyclin A that were consistent with the induction of cell cycle arrest in BEAS-2B cells exposed to prometryn. We also observed the increased formation of intracellular reactive oxygen species (ROS) in BEAS-2B cells, suggesting that this cell line is sensitive to prometryn. Finally, prometryn induced DNA double-strand breaks in BEAS-2B cells. In conclusion, prometryn affected key molecules involved in cell cycle regulation, induced oxidative stress, and induced DNA damage in BEAS-2B cells, which may shed light on the mechanism by which prometryn promotes lung cancer development.
扑灭津是一种毒性为低到中等的除草剂，属于三嗪类除草剂，这类除草剂在农业中广泛用于控制各种杂草的生长。尽管许多研究表明三嗪类除草剂对人类有致癌潜力，但扑灭津对人类细胞的细胞毒性作用及其潜在机制尚未完全了解。肺是环境污染物积累的最重要器官之一。本研究的目的是使用人支气管上皮细胞系BEAS-2B来确定扑灭津对正常肺细胞的细胞毒性作用。我们发现，高浓度的扑灭津处理会使BEAS-2B细胞生长停滞在S期，而低浓度时细胞周期不受影响。此外，我们观察到细胞周期蛋白依赖性激酶2（CDK2）和细胞周期蛋白A的表达水平发生了变化，这与暴露于扑灭津的BEAS-2B细胞中细胞周期停滞的诱导一致。我们还观察到BEAS-2B细胞内活性氧（ROS）的形成增加，表明该细胞系对扑灭津敏感。最后，扑灭津在BEAS-2B细胞中诱导了DNA双链断裂。总之，扑灭津影响了参与细胞周期调控的关键分子，诱导了氧化应激，并在BEAS-2B细胞中诱导了DNA损伤，这可能有助于揭示扑灭津促进肺癌发展的机制。
