Department of Chronic Disease Convergence Research, Division of Allergy and Respiratory Disease Research, Korea National Institute of Health, Chungju 28159, Korea.
Department of Materials science and Engineering, Yonsei University, Seoul 03722, Korea.
Biomolecules. 2021 Feb 16;11(2):291. doi: 10.3390/biom11020291.
Several epidemiological studies concluded that inhalation of diesel exhaust particles (DEP) is associated with an increase in the relative risk of lung cancer. In vitro research evaluating the genetic damage and/or changes in gene expression have been attempted to explain the relationship between DEP exposure and carcinogenicity. However, to date, investigations have been largely confined to studies in immortalized or tumorigenic epithelial cell models. Few studies have investigated damage at the chromosomal level to DEP exposure in normal cell lines. Here, we present the genotoxic effects of DEP in normal cells (embryonic human lung fibroblasts) by conventional genotoxicity testing (micronuclei (MN) and comet assay). We show the differentially expressed genes and enriched pathways in DEP-exposed WI-38 cells using RNA sequencing data. We observed a significant increase in single-strand DNA breaks and the frequency of MN in DEP-exposed cells in a dose-dependent manner. The differentially expressed genes following DEP exposure were significantly enriched in the pathway for responding to xenobiotics and DNA damage. Taken together, these results show that DEP exposure induced DNA damage at the chromosomal level in normal human lung cells and provide information on the expression of genes associated with genotoxic stress.
几项流行病学研究得出结论，吸入柴油机废气颗粒（DEP）会增加肺癌的相对风险。为了解释 DEP 暴露与致癌性之间的关系，已经尝试进行了评估遗传损伤和/或基因表达变化的体外研究。然而，迄今为止，调查主要局限于永生化或致瘤上皮细胞模型的研究。很少有研究调查正常细胞系中 DEP 暴露引起的染色体水平损伤。在这里，我们通过常规遗传毒性测试（微核（MN）和彗星试验）研究了 DEP 在正常细胞（人胚肺成纤维细胞）中的遗传毒性作用。我们使用 RNA 测序数据展示了 DEP 暴露后 WI-38 细胞中差异表达的基因和富集的途径。我们观察到 DEP 暴露的细胞中单链 DNA 断裂和 MN 频率呈剂量依赖性增加。DEP 暴露后差异表达的基因在对外源物和 DNA 损伤的反应途径中显著富集。总之，这些结果表明 DEP 暴露在正常人类肺细胞中引起了染色体水平的 DNA 损伤，并提供了与遗传毒性应激相关的基因表达信息。
