Particularly harmful particles? A study of airborne particles with a focus on genotoxicity and oxidative stress

Today it is well established that particulate matter (PM) cause a wide range of health effects. The underlying mechanisms likely include inflammation, oxidative stress and genotoxicity. There is however a lack of knowledge regarding how particles from different sources contribute to these effects. Furthermore, oxidative stress is difficult to analyse due to the risk of artificial oxidation during sample preparation and analysis.

The main aims of this thesis were to investigate different methods for analysis of oxidative DNA damage and to compare the ability of particles from different source to a) cause DNA damage, b) cause oxidation of DNA, c) induce inflammatory mediators, d) cause mitochondrial depolarisation and c) form intracellular reactive oxygen species (ROS).

In Paper I and II the background level of oxidative DNA damage in human lymphocytes was investigated. HPLC (high performance liquid chromatography) with electrochemical detection was used to analyse 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG) and the Comet assay in combination with the enzyme formamidopyrimidine glycosylase (FPG) was used to detect mainly oxidised purines. It was found that the level in a healthy Swedish population was around 1 8-oxodG per 106 dG measured using HPLCEC, and 0.24 FPG sites per 106 dG using the Comet assay. Furthermore, there was no correlation between the levels of 8-oxodG and FPG sites.

In Papers III-VI, the toxicity of particles from different sources were studied. It was found that subway particles were most genotoxic of all particles tested and that they caused formation of 8-oxodG and intracellular ROS in cultured human lung cells. In contrast, the street particles caused the highest release of inflammatory cytokines. Particles from tire-road wear collected using a road-simulator were genotoxic and induced inflammatory cytokines without involvement of particles related to vehicle exhaust. Furthermore, more efficient combustion of wood and pellet gave much less emissions of particles, but those emitted did not show less toxicity. Finally, diesel particles were most potent to cause mitochondrial damage, followed by PM from wood combustion and the subway.

In conclusion, PM from different sources showed different types of toxic effects. Subway particles were most potent regarding genotoxicity and oxidative stress in vitro, the main focus in this thesis, and may in this context therefore be regarded as "particularly harmful".

List of scientific papers

I. Gedik CM, Collins A; ESCODD (European Standards Committee on Oxidative DNA Damage) (1970). Establishing the background level of base oxidation in human lymphocyte DNA: results of an interlaboratory validation study. FASEB J. 19(1): 82-4.
https://pubmed.ncbi.nlm.nih.gov/15533950

II. Hofer T, Karlsson HL, Moller L (2006). DNA oxidative damage and strand breaks in young healthy individuals: a gender difference and the role of life style factors. Free Radic Res. 40(7): 707-14.
https://pubmed.ncbi.nlm.nih.gov/16983997

III. Karlsson HL, Nygren J, Moller L (2004). Genotoxicity of airborne particulate matter: the role of cell-particle interaction and of substances with adduct-forming and oxidizing capacity. Mutat Res. 565(1): 1-10.
https://pubmed.ncbi.nlm.nih.gov/15576234

IV. Karlsson HL, Nilsson L, Moller L (2005). Subway particles are more genotoxic than street particles and induce oxidative stress in cultured human lung cells. Chem Res Toxicol. 18(1): 19-23.
https://pubmed.ncbi.nlm.nih.gov/15651844

V. Karlsson HL, Ljungman AG, Lindbom J, Moller L (2006). Comparison of genotoxic and inflammatory effects of particles generated by wood combustion, a road simulator and collected from street and subway. Toxicol Lett. 165(3): 203-11.
https://pubmed.ncbi.nlm.nih.gov/16716543

VI. Karlsson HL, Holgersson Å, Möller L (2006). The ability of particles from different sources to induce mitochondrial damage and intracellular reactive oxygen species. [Submitted]