UVB irradiation changes genotoxic potential of nonylphenolpolyethoxylates-remarkable generation of γ-H2AX with degradation of chemical structure.
UVB irradiation changes genotoxic potential of nonylphenolpolyethoxylates-remarkable generation of γ-H2AX with degradation of chemical structure.
复制标题
UVB 照射改变了壬基酚聚乙氧基化物的潜在遗传毒性——显着生成 γ-H2AX，同时化学结构发生降解。
DOI：
10.1093/mutage/ges043
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Ibuki Y.
中科院分区：
文献类型：
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作者：
Toyooka T;Kubota T;Ibuki Y.
壬基酚醛聚氧乙烯酯（NPEOs）是一种非离子表面活性剂，广泛用于工业和家庭用途。在实际环境中，npeo可以被生物降解，但据报道其产物比母体化合物更具持久性和毒性。npeo也暴露在阳光下并降解。对npeo光降解的研究主要集中在光照后的化学变化。光降解产物的毒性变化与化学变化之间的关系尚不完全清楚。在这项研究中，我们基于组蛋白H2AX （γ-H2AX）的磷酸化，研究了uvb照射下具有环氧乙烷单位15和70的NPEOs对人乳腺腺癌细胞系MCF-7的遗传毒性，这是DNA损伤的敏感标记。我们澄清了UVB照射极大地改变了NPEO的遗传毒性潜能：NPEO（15）产生γ-H2AX的能力显著降低，而非基因毒性的NPEO（70）能够产生γ-H2AX。流式细胞分析表明，uvb辐照NPEO（70）产生的γ-H2AX与细胞周期相独立。此外，它的产生还涉及到ATM或DNA- pk的激活，这是一种响应DNA双链断裂的一般信号通路。高效液相色谱分析表明，侧链较短的NPEO中间体（15）的形成是γ-H2AX生成的原因。这项研究表明，在进行环境污染物风险评估时，应考虑光降解中间体的遗传毒性。
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.