Abstract
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.
Highlights
In recent decades, various studies have been conducted on the effects of particulate matter (PM) on human health
We aim to provide a meaningful interpretation of genotoxicity using cytogenetic or gene expression markers induced by diesel exhaust particles (DEP) in human normal lung cells as a model of pulmonary tissue
We show that DNA strand breakage and micronucleus induction are induced in normal cells after exposure to well-characterized standard DEP (NIST 1650b)
Summary
Various studies have been conducted on the effects of particulate matter (PM) on human health. There is epidemiological evidence regarding potential causal relations between inhaled exposures of PM and adverse health outcomes [1,2]. Fine particles (diameters < 2.5 μm (PM2.5 )) penetrate the respiratory tract and bloodstream due to their small size and large surface area at the same mass and increases the risk of cardiovascular and respiratory disease [3,4]. DEP are known as a pulmonary carcinogen on the basis of sufficient evidence showing that exposure is associated with an increased risk for lung cancer [5,6].
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