Bao Lingzhi, Xu An, Tong Liping, Chen Shaopeng, Zhu Lingyan, Zhao Ye, Zhao Guoping, Jiang Erkang, Wang Jun, Wu Lijun
Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, Anhui, People's Republic of China.
Environ Health Perspect. 2009 Mar;117(3):436-41. doi: 10.1289/ehp.0800029. Epub 2008 Sep 15.
Diesel exhaust [diesel exhaust particles (DEPs) and their extracts (DPE)] and ultraviolet A radiation (UVA) are two ubiquitous environmental factors that have been identified as essential risk factors for various benign or malignant human diseases, either alone or in combination with other agents.
We aimed to investigate the synergistic effects of DPE and UVA at low-dose exposures in human-hamster hybrid (AL) cells and their underlying mechanisms.
We exposed exponentially growing AL cells to DPE and/or UVA radiation with or without reactive oxygen species (ROS) quenchers and then assayed the cells for survival, mutation induction, apoptosis, and micronucleus generation. In addition, using a singlet oxygen (1O2) trapping probe, 2,2,6,6-tetramethyl-4-piperidone, coupled with electron paramagnetic resonance spectroscopy, we determined the production of 1O2.
Treatment of AL cells with DPE+UVA induced significant cytotoxic and genotoxic damage. In contrast, we found no significant damage in cells treated with either UVA or DPE alone at the same doses. Mutation spectra of CD59- mutants showed that treatment with DPE+UVA easily induces multilocus deletions. Sodium azide significantly inhibited both cellular and DNA damage induced by DPE+UVA treatment, whereas other ROS inhibitors had little protecting effect. Furthermore, we found a significant increase of 1O2 in the cells that received DPE+UVA treatment.
These findings suggest that UVA activated the genotoxicity and cytotoxicity of DPE in mammalian cells and that 1O2 played an important role in these processes.
柴油废气[柴油废气颗粒（DEP）及其提取物（DPE）]和紫外线A辐射（UVA）是两种普遍存在的环境因素，已被确定为人类各种良性或恶性疾病的重要危险因素，可单独或与其他因素联合作用。
我们旨在研究低剂量暴露下DPE和UVA在人-仓鼠杂交（AL）细胞中的协同作用及其潜在机制。
将指数生长的AL细胞暴露于DPE和/或UVA辐射下，同时添加或不添加活性氧（ROS）淬灭剂，然后检测细胞的存活率、突变诱导率、凋亡率和微核发生率。此外，我们使用单线态氧（1O2）捕获探针2,2,6,6-四甲基-4-哌啶酮，结合电子顺磁共振光谱，测定1O2的产生。
用DPE+UVA处理AL细胞会诱导显著的细胞毒性和遗传毒性损伤。相比之下，我们发现在相同剂量下单独用UVA或DPE处理的细胞没有显著损伤。CD59-突变体的突变谱表明，用DPE+UVA处理容易诱导多位点缺失。叠氮化钠显著抑制了DPE+UVA处理诱导的细胞和DNA损伤，而其他ROS抑制剂几乎没有保护作用。此外，我们发现接受DPE+UVA处理的细胞中1O2显著增加。
这些发现表明，UVA激活了DPE在哺乳动物细胞中的遗传毒性和细胞毒性，并且1O2在这些过程中起重要作用。
