Mechanisms Related to the Genotoxicity of Particles in the Subway

Feb 9, 2008 - Another source of importance for certain populations is exposure to particles in subway systems. We recently reported that these particl...
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Chem. Res. Toxicol. 2008, 21, 726–731

Mechanisms Related to the Genotoxicity of Particles in the Subway and from Other Sources Hanna L. Karlsson,† Åsa Holgersson,‡,§ and Lennart Möller*,† Unit for Analytical Toxicology, Department of Biosciences and Nutrition at NoVum, Karolinska Institutet, SE-141 57 Huddinge, Stockholm, Sweden, and Unit of Medical Radiation Biology, Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, SE-171 76 Stockholm, Sweden ReceiVed October 1, 2007

Negative health effects of airborne particles have clearly been shown in epidemiological studies. People get exposed to particles from various sources such as the combustion of, for example, diesel and wood and also from particles arising from tire-road wear. Another source of importance for certain populations is exposure to particles in subway systems. We recently reported that these particles were more genotoxic when compared to that of several other particle types. The aim of this study was to further investigate and compare the toxicity of subway particles and particles from other sources as well as investigate some mechanisms behind the genotoxicity of subway particles. This was done by comparing the ability of subway particles and particles from a street, pure tire-road wear particles, and particles from wood and diesel combustion to cause mitochondrial depolarization and to form intracellular reactive oxygen species (ROS). Furthermore, the genotoxicity and ability to cause oxidative stress was compared to magnetite particles since this is a main component in subway particles. It was concluded that the subway particles and also street particles and particles from wood and diesel combustion caused mitochondrial depolarization. The ability to damage the mitochondria is thus not the only explanation for the high genotoxicity of subway particles. Subway particles also formed intracellular ROS. This effect may be part of the explanation as to why subway particles show such high genotoxicity when compared to that of other particles. Genotoxicity can, however, not be explained by the main component, magnetite, by water-soluble metals, or by intracellular mobilized iron. The genotoxicity is most likely caused by highly reactive surfaces giving rise to oxidative stress. 1. Introduction Several epidemiological studies show that morbidity and mortality follow exposure to particles, especially fine particles, often measured as particulate matter (PM1) with a diameter less than 2.5 µm (PM2.5). The adverse health effects include exacerbation of asthma and chronic obstructive pulmonary disease (COPD) (1, 2) as well as death in lung cancer and cardiovascular diseases (3, 4). The mechanisms behind these effects are considered to involve oxidative stress and inflammation (5, 6). Reactive oxygen species (ROS) are formed by inflammatory cells as part of the defense against microorganisms, but can also be formed by the particle itself via radicals on the surface, surface bound chemicals, or via transition metals (7–9). Surface bound chemicals include quinones, which can undergo redox cycling (10) and thereby generate super oxide anions (•O2-) and hydrogen peroxide that in combination with transition metals such as Fe2+ can form hydroxyl radicals (•OH) via Fenton-catalyzed Haber-Weiss reactions. If these radicals * To whom correspondence should be addressed. Professor Lennart Möller, Department of Biosciences and Nutrition at Novum, Karolinska Institutet, SE-141 57 Huddinge, Stockholm, Sweden. Tel: +46 8 608 91 89. Fax: + 46 8 774 68 3. E-mail: [email protected]. † Unit for Analytical Toxicology. ‡ Unit of Medical Radiation Biology. § Current address: Roche AB, P.O. Box 47327, SE-100 74 Stockholm, Sweden. 1 Abbreviations: ALS, alkaline labile sites; COPD, chronic obstructive pulmonary disease; DCFH-DA, 2′,7′-dichlorofluorescin diacetate; FPG, formamidopyrimidine DNA glycosylase; PM, particulate matter; ROS, reactive oxygen species; SSB, single strand breaks; TMRE, tetramethylrhodamine ethyl ester; 8-oxodG, 8-oxo-7,8-dihydro-2’-deoxyguanosine.

are formed close to DNA, which is possible since the electronrich structure of DNA attracts positively charged metal ions, they may react and form DNA adducts such as 8-oxo-7,8dihydro-2′-deoxyguanosine (8-oxodG). Studies on cultured human lung cells have shown that particles from various sources cause DNA damage and oxidative stress due to soluble metals, polyaromatic hydrocarbons (PAHs), or the particle core (11–15). Furthermore, oxidative DNA damage in human blood cells have been associated with personal exposure to PM2.5 and to ultrafine particles (particles