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Prometryn induces apoptotic cell death through cell cycle arrest and oxidative DNA damage.
Toxicology Research ( IF 2.1 ) Pub Date : 2019-07-26 , DOI: 10.1039/c9tx00080a
Qiaoyun Liu 1 , Longsheng Wang 2 , Hanwen Chen 1, 3 , Bo Huang 1 , Jiawei Xu 1 , Ying Li 4 , Paul Héroux 4 , Xinqiang Zhu 5 , Yihua Wu 1 , Dajing Xia 1
Affiliation  

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.

中文翻译:

Prometryn通过细胞周期停滞和氧化性DNA损伤诱导凋亡性细胞死亡。

Prometryn是一种轻度到中度毒性的除草剂,属于除草剂三嗪类,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具有致癌作用,但尚未完全了解脯氨酰胺对人细胞的细胞毒性作用以及这些作用的潜在机制。肺是积累环境污染物的最重要器官之一。这项研究的目的是确定使用人类支气管上皮细胞系BEAS-2B的普罗萘酮对正常肺细胞的细胞毒性作用。我们发现,用高浓度的前metry草素处理可阻止BEAS-2B细胞在S期生长,而在低浓度下,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,这些变化与暴露于prometryn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细胞中细胞内活性氧(ROS)形成的增加,表明该细胞系对prometricn敏感。最终,prometricn在BEAS-2B细胞中诱导了DNA双链断裂。综上所述,脯氨酰胺影响了BEAS-2B细胞中参与细胞周期调控,诱导的氧化应激和DNA损伤的关键分子,这可能揭示了脯氨酰胺促进肺癌发展的机制。我们还观察到BEAS-2B细胞中细胞内活性氧(ROS)形成的增加,表明该细胞系对prometricn敏感。最终,prometricn在BEAS-2B细胞中诱导了DNA双链断裂。综上所述,脯氨酰胺影响了BEAS-2B细胞中参与细胞周期调控,诱导的氧化应激和DNA损伤的关键分子,这可能揭示了脯氨酰胺促进肺癌发展的机制。我们还观察到BEAS-2B细胞中细胞内活性氧(ROS)形成的增加,表明该细胞系对prometricn敏感。最终,prometricn在BEAS-2B细胞中诱导了DNA双链断裂。综上所述,脯氨酰胺影响了BEAS-2B细胞中参与细胞周期调控,诱导的氧化应激和DNA损伤的关键分子,这可能揭示了脯氨酰胺促进肺癌发展的机制。
更新日期:2019-07-26
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