Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Science, Shantou University, Shantou, Guangdong 515063, China; Southern Marine Science and Engineering Guangdong Laboratory, Guangzhou 511458, China.
Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Science, Shantou University, Shantou, Guangdong 515063, China; Southern Marine Science and Engineering Guangdong Laboratory, Guangzhou 511458, China.
Sci Total Environ. 2022 Feb 10;807(Pt 1):150561. doi: 10.1016/j.scitotenv.2021.150561. Epub 2021 Sep 24.
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.
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累积。尽管 6-OH-BDE-47 在鲸类动物中经常大量检出，但它的潜在毒性作用在很大程度上是未知的。我们通过将 6-OH-BDE-47 暴露于浓度范围为 0.02、0.2、2 至 4 μM 的 pygmy killer whale skin fibroblast cell lines (PKW-LWHT) 中，来探索 OH-BDEs 的毒理学途径和机制。结果表明，6-OH-BDE-47 以浓度和时间依赖的方式抑制细胞增殖。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 分析，我们发现 6-OH-BDE-47 上调了 p21 和 RB1 的转录和表达水平，并下调了增殖细胞核抗原（PCNA）、CDK2、CDK4、cyclin D1、cyclin E2、E2F1 和 E2F3 的表达水平以及细胞中磷酸化 RB1 的表达水平。结果表明，6-OH-BDE-47 通过改变 G1 期相关调节基因的表达水平，能够将 PKW-LWHT 细胞的细胞周期阻滞在 G1 期，最终抑制细胞增殖。
