Chronic polycyclic aromatic hydrocarbon exposure causes DNA damage and genomic instability in lung epithelial cells

ABSTRACTAlthough DNA repair proteins in bacteria are critical for pathogens' genome stability and for subverting the host defense, the role of host DNA repair proteins in response to bacterial infection is poorly defined. Here, we demonstrate, for the first time, that infection with the Gram-negative bacteriumPseudomonas aeruginosasignificantly altered the expression and enzymatic activity of 8-oxoguanine DNA glycosylase (OGG1) in lung epithelial cells. Downregulation of OGG1 by a small interfering RNA strategy resulted in severe DNA damage and cell death. In addition, acetylation of OGG1 is required for host responses to bacterial genotoxicity, as mutations of OGG1 acetylation sites increased Cockayne syndrome group B (CSB) protein expression. These results also indicate that CSB may be involved in DNA repair activity during infection. Furthermore, OGG1 knockout mice exhibited increased lung injury after infection withP. aeruginosa, as demonstrated by higher myeloperoxidase activity and lipid peroxidation. Together, our studies indicate thatP. aeruginosainfection induces significant DNA damage in host cells and that DNA repair proteins play a critical role in the host response toP. aeruginosainfection, serving as promising targets for the treatment of this condition and perhaps more broadly Gram-negative bacterial infections.

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Oxidative Mitochondrial DNA Damage in Lung Epithelial Cells Induced by Non-Pore-Forming Action of the Pneumococcal Virulence Factor Pneumolysin

10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a3895 ◽

2021 ◽

Author(s):

N.M. Maurice ◽

B. Bedi ◽

Z. Yuan ◽

M. Koval ◽

J.E. Vidal ◽

...

Keyword(s):

Dna Damage ◽

Mitochondrial Dna ◽

Epithelial Cells ◽

Virulence Factor ◽

Lung Epithelial Cells ◽

Mitochondrial Dna Damage ◽

Lung Epithelial

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Cytotoxic Effects of Air Freshener Biocides in Lung Epithelial Cells

Natural Product Communications ◽

10.1177/1934578x1300800929 ◽

2013 ◽

Vol 8 (9) ◽

pp. 1934578X1300800

Author(s):

Jung-Taek Kwon ◽

Mimi Lee ◽

Gun-Baek Seo ◽

Hyun-Mi Kim ◽

Ilseob Shim ◽

...

Keyword(s):

Dna Damage ◽

Epithelial Cells ◽

Cell Viability ◽

Lung Epithelial Cells ◽

Ros Generation ◽

Dependent Manner ◽

Cytotoxic Effects ◽

Lung Epithelial ◽

Dose Dependent ◽

A549 Lung

This study evaluated the cytotoxicity of mixtures of citral (CTR) and either benzisothiazolinone (BIT, Mix-CTR-BIT) or triclosan (TCS, Mix-CTR-TCS) in human A549 lung epithelial cells. We investigated the effects of various mix ratios of these common air freshener ingredients on cell viability, cell proliferation, reactive oxygen species (ROS) generation, and DNA damage. Mix-CTR-BIT and Mix-CTR-TCS significantly decreased the viability of lung epithelial cells and inhibited cell growth in a dose-dependent manner. In addition, both mixtures increased ROS generation, compared to that observed in control cells. In particular, cell viability, growth, and morphology were affected upon increase in the proportion of BIT or TCS in the mixture. However, comet analysis showed that treatment of cells with Mix-CTR-BIT or Mix-CTR-TCS did not increase DNA damage. Taken together, these data suggested that increasing the content of biocides in air fresheners might induce cytotoxicity, and that screening these compounds using lung epithelial cells may contribute to hazard assessment.

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