Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages. / Jantzen, Kim; Roursgaard, Martin; Madsen, Claus Desler; Loft, Steffen; Rasmussen, Lene Juel; Møller, Peter.

In: Mutagenesis, Vol. 27, No. 6, 11.2012, p. 693-701.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Jantzen, K, Roursgaard, M, Madsen, CD, Loft, S, Rasmussen, LJ & Møller, P 2012, 'Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages', Mutagenesis, vol. 27, no. 6, pp. 693-701. https://doi.org/10.1093/mutage/ges035

APA

Jantzen, K., Roursgaard, M., Madsen, C. D., Loft, S., Rasmussen, L. J., & Møller, P. (2012). Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages. Mutagenesis, 27(6), 693-701. https://doi.org/10.1093/mutage/ges035

Vancouver

Jantzen K, Roursgaard M, Madsen CD, Loft S, Rasmussen LJ, Møller P. Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages. Mutagenesis. 2012 Nov;27(6):693-701. https://doi.org/10.1093/mutage/ges035

Author

Jantzen, Kim ; Roursgaard, Martin ; Madsen, Claus Desler ; Loft, Steffen ; Rasmussen, Lene Juel ; Møller, Peter. / Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages. In: Mutagenesis. 2012 ; Vol. 27, No. 6. pp. 693-701.

Bibtex

@article{d61d1c8bf089421bb2911c37a893f727,
title = "Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages",
abstract = "Studies in mono-culture of cells have shown that diesel exhaust particles (DEPs) increase the production of reactive oxygen species (ROS) and oxidative stress-related damage to DNA. However, the level of particle-generated genotoxicity may depend on interplay between different cell types, e.g. lung epithelium and immune cells. Macrophages have important immune defence functions by engulfing insoluble foreign materials, including particles, although they might also promote or enhance inflammation. We investigated the effect of co-culturing type II lung epithelial A549 cells with macrophages upon treatment with standard reference DEPs, SRM2975 and SRM1650b. The exposure to DEPs did not affect the colony-forming ability of A549 cells in co-culture with THP-1a cells. The DEPs generated DNA strand breaks and oxidatively damaged DNA, measured using the alkaline comet assay as formamidopyrimidine-DNA glycosylase or oxoguanine DNA glycosylase (hOGG1) sensitive sites, in mono-cultures of A549 or THP-1a and co-cultures of A549 and THP-1a cells. The strongest genotoxic effects were observed in A549 mono-cultures and SRM2975 was more potent than SRM1650b. The ROS production only increased in cells exposed to SRM2975, with strongest concentration-dependent effect in the THP-1a mono-cultures. The basal respiration level in THP-1a cells increased on exposure to SRM1650b and SRM2975 without indication of mitochondrial dysfunction. This is consistent with activation of the cells and there was no direct relationship between levels of respiration and ROS production. In conclusion, exposure of mono-cultured cells to DEPs generated oxidative stress to DNA, whereas co-cultures with macrophages had lower levels of oxidatively damaged DNA than A549 epithelial cells.",
author = "Kim Jantzen and Martin Roursgaard and Madsen, {Claus Desler} and Steffen Loft and Rasmussen, {Lene Juel} and Peter M{\o}ller",
year = "2012",
month = "11",
doi = "10.1093/mutage/ges035",
language = "English",
volume = "27",
pages = "693--701",
journal = "Mutagenesis",
issn = "0267-8357",
publisher = "Oxford University Press",
number = "6",

}

RIS

TY - JOUR

T1 - Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages

AU - Jantzen, Kim

AU - Roursgaard, Martin

AU - Madsen, Claus Desler

AU - Loft, Steffen

AU - Rasmussen, Lene Juel

AU - Møller, Peter

PY - 2012/11

Y1 - 2012/11

N2 - Studies in mono-culture of cells have shown that diesel exhaust particles (DEPs) increase the production of reactive oxygen species (ROS) and oxidative stress-related damage to DNA. However, the level of particle-generated genotoxicity may depend on interplay between different cell types, e.g. lung epithelium and immune cells. Macrophages have important immune defence functions by engulfing insoluble foreign materials, including particles, although they might also promote or enhance inflammation. We investigated the effect of co-culturing type II lung epithelial A549 cells with macrophages upon treatment with standard reference DEPs, SRM2975 and SRM1650b. The exposure to DEPs did not affect the colony-forming ability of A549 cells in co-culture with THP-1a cells. The DEPs generated DNA strand breaks and oxidatively damaged DNA, measured using the alkaline comet assay as formamidopyrimidine-DNA glycosylase or oxoguanine DNA glycosylase (hOGG1) sensitive sites, in mono-cultures of A549 or THP-1a and co-cultures of A549 and THP-1a cells. The strongest genotoxic effects were observed in A549 mono-cultures and SRM2975 was more potent than SRM1650b. The ROS production only increased in cells exposed to SRM2975, with strongest concentration-dependent effect in the THP-1a mono-cultures. The basal respiration level in THP-1a cells increased on exposure to SRM1650b and SRM2975 without indication of mitochondrial dysfunction. This is consistent with activation of the cells and there was no direct relationship between levels of respiration and ROS production. In conclusion, exposure of mono-cultured cells to DEPs generated oxidative stress to DNA, whereas co-cultures with macrophages had lower levels of oxidatively damaged DNA than A549 epithelial cells.

AB - Studies in mono-culture of cells have shown that diesel exhaust particles (DEPs) increase the production of reactive oxygen species (ROS) and oxidative stress-related damage to DNA. However, the level of particle-generated genotoxicity may depend on interplay between different cell types, e.g. lung epithelium and immune cells. Macrophages have important immune defence functions by engulfing insoluble foreign materials, including particles, although they might also promote or enhance inflammation. We investigated the effect of co-culturing type II lung epithelial A549 cells with macrophages upon treatment with standard reference DEPs, SRM2975 and SRM1650b. The exposure to DEPs did not affect the colony-forming ability of A549 cells in co-culture with THP-1a cells. The DEPs generated DNA strand breaks and oxidatively damaged DNA, measured using the alkaline comet assay as formamidopyrimidine-DNA glycosylase or oxoguanine DNA glycosylase (hOGG1) sensitive sites, in mono-cultures of A549 or THP-1a and co-cultures of A549 and THP-1a cells. The strongest genotoxic effects were observed in A549 mono-cultures and SRM2975 was more potent than SRM1650b. The ROS production only increased in cells exposed to SRM2975, with strongest concentration-dependent effect in the THP-1a mono-cultures. The basal respiration level in THP-1a cells increased on exposure to SRM1650b and SRM2975 without indication of mitochondrial dysfunction. This is consistent with activation of the cells and there was no direct relationship between levels of respiration and ROS production. In conclusion, exposure of mono-cultured cells to DEPs generated oxidative stress to DNA, whereas co-cultures with macrophages had lower levels of oxidatively damaged DNA than A549 epithelial cells.

U2 - 10.1093/mutage/ges035

DO - 10.1093/mutage/ges035

M3 - Journal article

C2 - 22869610

VL - 27

SP - 693

EP - 701

JO - Mutagenesis

JF - Mutagenesis

SN - 0267-8357

IS - 6

ER -

ID: 40840828