Synergistic effects induced by a low dose of diesel particulate extract and ultraviolet-A in Caenorhabditis elegans: DNA damage-triggered germ cell apoptosis.
Synergistic effects induced by a low dose of diesel particulate extract and ultraviolet-A in Caenorhabditis elegans: DNA damage-triggered germ cell apoptosis.
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低剂量柴油颗粒提取物和紫外线 A 对秀丽隐杆线虫的协同作用：DNA 损伤引发的生殖细胞凋亡
DOI：
10.1021/tx500137f
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发表时间：
2014-06-16
影响因子：
4.1
通讯作者：
Wu, Lijun
中科院分区：
文献类型：
--
作者：
Guo, Xiaoying;Bian, Po;Liang, Junting;Wang, Yichen;Li, Luzhi;Wang, Jun;Yuan, Hang;Chen, Shaopeng;Xu, An;Wu, Lijun
柴油机尾气已被列为潜在致癌物，并与多种健康影响有关。先前的一项研究表明，当柴油机尾气与细胞系统中的紫外线 A (UVA) 共同暴露时，可以减少表现出诱变效应的剂量。然而，协同作用的机制仍有待阐明，特别是在体内系统中。在本研究中，我们使用秀丽隐杆线虫 (C. elegans) 作为体内系统，研究了柴油颗粒提取物 (DPE) 和 UVA 的协同效应，并使用相关突变体从基因角度剖析了其潜在机制。我们的结果表明，尽管将年轻成虫阶段的野生型线虫同时暴露于低剂量的 DPE (20 μg/mL) 加 UVA (0.2、0.5 和 1.0 J/cm2) 不会影响线虫的发育（有丝分裂生殖细胞和幼虫大小），但会导致生殖细胞死亡的显着诱导。使用 hus-1::gfp 菌株，在增殖的生殖细胞中观察到 HUS-1::GFP 的明显焦点，表明用 DPE 加 UVA 处理线虫后 DNA 受到损伤。此外，在核心凋亡、检查点 HUS-1、CEP-1/p53 和 MAPK 依赖性信号通路的单基因功能丧失突变中，DPE 联合 UVA 诱导的生殖细胞死亡得到了缓解。使用活性氧 (ROS) 探针发现，同时暴露于 DPE 和 UVA 的线虫体内 ROS 的产生量呈时间依赖性增加。此外，采用单线态氧 (1O2) 捕获探针 2,2,6,6-四甲基-4-哌啶酮，结合电子自旋共振分析，我们证明了同时暴露于 DPE 和 UVA 的蠕虫中 1O2 产量增加。这些结果表明，低剂量的UVA可以通过DNA损伤触发途径增强DPE的凋亡诱导，并且ROS的产生，特别是1O2，在启动协同过程中发挥着关键作用。
Diesel exhaust has been classified as a potential carcinogen and is associated with various health effects. A previous study showed that the doses for manifesting the mutagenetic effects of diesel exhaust could be reduced when coexposed with ultraviolet-A (UVA) in a cellular system. However, the mechanisms underlying synergistic effects remain to be clarified, especially in an in vivo system. In the present study, using Caenorhabditis elegans (C. elegans) as an in vivo system we studied the synergistic effects of diesel particulate extract (DPE) plus UVA, and the underlying mechanisms were dissected genetically using related mutants. Our results demonstrated that though coexposure of wild type worms at young adult stage to low doses of DPE (20 μg/mL) plus UVA (0.2, 0.5, and 1.0 J/cm2) did not affect worm development (mitotic germ cells and brood size), it resulted in a significant induction of germ cell death. Using the strain of hus-1::gfp, distinct foci of HUS-1::GFP was observed in proliferating germ cells, indicating the DNA damage after worms were treated with DPE plus UVA. Moreover, the induction of germ cell death by DPE plus UVA was alleviated in single-gene loss-of-function mutations of core apoptotic, checkpoint HUS-1, CEP-1/p53, and MAPK dependent signaling pathways. Using a reactive oxygen species (ROS) probe, it was found that the production of ROS in worms coexposed to DPE plus UVA increased in a time-dependent manner. In addition, employing a singlet oxygen (1O2) trapping probe, 2,2,6,6-tetramethyl-4-piperidone, coupled with electron spin resonance analysis, we demonstrated the increased 1O2 production in worms coexposed to DPE plus UVA. These results indicated that UVA could enhance the apoptotic induction of DPE at low doses through a DNA damage-triggered pathway and that the production of ROS, especially 1O2, played a pivotal role in initiating the synergistic process.
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DOI：
10.1006/mcbr.2001.0300
发表时间：
2001-11-01
期刊：
Molecular Cell Biology Research Communications
影响因子：
--
作者：
Berman, Kevin;McKay, Jim;Cobb, Melanie
通讯作者：
Cobb, Melanie
影响因子：
16
作者：
Gartner, A;Milstein, S;Hengartner, MO
通讯作者：
Hengartner, MO
DOI：
10.1164/rccm.200402-248oc
发表时间：
2005-02-15
影响因子：
24.7
作者：
Arimoto, T;Kadiiska, MB;Mason, RP
通讯作者：
Mason, RP
影响因子：
64.8
作者：
Artal-Sanz, Marta;Tavernarakis, Nektarios
通讯作者：
Tavernarakis, Nektarios
DOI：
10.1159/000064535
发表时间：
2002-09-01
期刊：
SKIN PHARMACOLOGY AND APPLIED SKIN PHYSIOLOGY
影响因子：
--
作者：
de Gruijl, FR
通讯作者：
de Gruijl, FR