Synergistic Effects Induced by a Low Dose of Diesel Particulate Extract and Ultraviolet-A in Caenorhabditis elegans : DNA Damage-Triggered Germ Cell Apoptosis

作者：Xiaoying Guo, Po Bian, Junting Liang, Yichen Wang, Luzhi Li, Jun Wang, Hang Yuan, Shaopeng Chen, An Xu, Lijun Wu · 发表于：Chemical Research in Toxicology · 年份：2014 · DOI：10.1021/tx500137f · 被引用次数：30 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、Air Quality and Health Impacts、Circadian rhythm and melatonin

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 (1O...