Institute for Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-shi, Shizuoka 422-8526, Japan.
Mutagenesis. 2013 Jan;28(1):7-14. doi: 10.1093/mutage/ges043. Epub 2012 Sep 17.
Nonylphenolpolyethoxylates (NPEOs) are non-ionic surfactants widely used for industrial and household purposes. In actual environments, NPEOs can be biodegraded, but the products are reported to be more persistent and toxic than the parent compounds. NPEOs are also exposed to sunlight and degraded. Studies on the photodegradation of NPEOs have focused mainly on chemical changes after exposure to light. Toxic changes of photodegraded products correlating to the chemical changes are not completely understood. In this study, we examined the genotoxicity of UVB-irradiated NPEOs having ethylene oxide units 15 and 70 in a human breast adenocarcinoma cell line, MCF-7, based on the phosphorylation of histone H2AX (γ-H2AX), a sensitive marker for DNA damage. We clarified that UVB irradiation drastically changed the genotoxic potential of NPEOs: NPEO(15)'s ability to generate γ-H2AX was significantly reduced, whereas non-genotoxic NPEO(70) became able to generate γ-H2AX. Flow cytometric analysis showed that the γ-H2AX generated by UVB-irradiated NPEO(70)was produced independent of cell cycle phases. In addition, its production involved the activation of ATM or DNA-PK, a general signalling pathway in response to DNA double strand breaks. High-performance liquid chromatography analysis indicated that the formation of NPEO intermediates with a short side-chain like NPEO(15) was the cause of the γ-H2AX generation. This study suggests the importance of taking the genotoxicity of photodegraded intermediates into consideration when conducting risk assessments of environmental pollutants.
壬基酚聚氧乙烯醚(NPEOs)是非离子表面活性剂,广泛用于工业和家庭用途。在实际环境中,NPEOs 可被生物降解,但据报道,其降解产物比母体化合物更持久且毒性更大。NPEOs 也会受到阳光照射而降解。关于 NPEOs 的光降解研究主要集中在暴露于光后发生的化学变化上。与化学变化相关的光降解产物的毒性变化尚未完全了解。在这项研究中,我们基于人乳腺癌腺癌细胞系 MCF-7 中组蛋白 H2AX(γ-H2AX)的磷酸化,研究了具有 15 和 70 个环氧乙烷单元的 UVB 辐照 NPEOs 的遗传毒性。γ-H2AX 是 DNA 损伤的敏感标志物。我们证实,UVB 照射极大地改变了 NPEOs 的遗传毒性潜力:NPEO(15) 生成 γ-H2AX 的能力显著降低,而无遗传毒性的 NPEO(70) 则能够生成 γ-H2AX。流式细胞术分析表明,UVB 辐照 NPEO(70)产生的 γ-H2AX 与细胞周期无关。此外,其产生涉及 ATM 或 DNA-PK 的激活,这是对 DNA 双链断裂的一般信号通路。高效液相色谱分析表明,形成具有像 NPEO(15) 这样短侧链的 NPEO 中间体是生成 γ-H2AX 的原因。本研究提示在进行环境污染物风险评估时,考虑光降解中间产物的遗传毒性的重要性。