6-OH-BDE-47 inhibited proliferation of skin fibroblasts from pygmy killer whale by inducing cell cycle arrest.
6-OH-BDE-47 inhibited proliferation of skin fibroblasts from pygmy killer whale by inducing cell cycle arrest.
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DOI：
10.1016/j.scitotenv.2021.150561
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发表时间：
2021-09
期刊：
影响因子：
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通讯作者：
Tong Li;Yajing Sun;Ying Zeng;E. Sanganyado;Bo Liang;Wenhua Liu
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作者：
Tong Li;Yajing Sun;Ying Zeng;E. Sanganyado;Bo Liang;Wenhua Liu
羟基化多溴二苯醚（OH-BDEs）是多溴二苯醚的主要转化产物，容易在海洋食物网中生物积累。虽然6-OH-BDE-47在鲸类动物中经常被大量检测到，但其潜在的毒性作用在很大程度上是未知的。我们通过将6-OH-BDE-47暴露于浓度为0.02、0.2、2至4 μM的俾格米虎鲸皮肤成纤维细胞系（PKW-LWHT）中，探讨了oh - bde -47的毒理学途径和机制。结果表明，6-OH-BDE-47对细胞增殖的抑制作用呈浓度依赖性和时间依赖性。细胞周期数据显示，6-OH-BDE-47将细胞周期阻滞在G0/G1期。通过qPCR和Western blot检测，我们发现6-OH-BDE-47上调p21和RB1的转录和表达水平，下调增殖细胞核抗原（PCNA）、CDK2、CDK4、细胞周期蛋白D1、细胞周期蛋白E2、E2F1、E2F3和细胞磷酸化RB1的表达水平。结果表明，6-OH-BDE-47能够通过改变G1期相关调控基因的表达水平，将PKW-LWHT细胞周期阻滞在G1期，最终抑制细胞增殖。
Hydroxylated polybrominated diphenyl ethers (OH-BDEs) are major transformation products of PBDEs that readily bioaccumulate in the marine food web. Although 6-OH-BDE-47 is frequently and abundantly detected in cetaceans, its potential toxic effects are largely unknown. We explored the toxicological pathways and mechanisms of OH-BDEs by exposing pygmy killer whale skin fibroblast cell lines (PKW-LWHT) to 6-OH-BDE-47 at concentrations ranging from 0.02, 0.2, 2 to 4 μM. The result showed that 6-OH-BDE-47 inhibited cell proliferation in a concentration- and time-dependent manner. The cell cycle data revealed that the cell cycle was arrest at the G0/G1 phase by 6-OH-BDE-47. Using qPCR and Western blot assay, we found that 6-OH-BDE-47 up-regulated the transcription and expression level of p21 and RB1 and down-regulated the expression level of Proliferating Cell Nuclear Antigen (PCNA), CDK2, CDK4, cyclin D1, cyclin E2, E2F1, and E2F3 and the cellular phosphorylated RB1. The results showed that 6-OH-BDE-47 was able to arrest the cell cycle of PKW-LWHT cells at G1 phase by changing the expression level of related regulatory genes in G1 stage, and finally inhibit cell proliferation.