Short Communication Transition Metals in Personal Samples of PM 2.5 and Oxidative Stress in Human Volunteers Mette Sørensen, 1 Roel P.F. Schins, 2 Ole Hertel, 3 and Steffen Loft 1 1 Institute of Public Health, University of Copenhagen, Copenhagen, Denmark; 2 Particle Research, Institut fu ¨ r Umweltmedizinische Forschung, Heinrich-Heine University, Du ¨ sseldorf, Germany; and 3 National Environmental Research Institute, Department of Atmospheric Environment, Roskilde, Denmark Abstract Ambient particulate matter (PM) has been associated with increased risk of lung cancer. One proposed mechanism is that PM induces oxidative stress mediated by transition metals contained within this mixture. We examined the relationship between the personal exposure to water- soluble transition metals in PM 2.5 and oxidative DNA damage. In 49 students from central Copenhagen, we determined PM 2.5 exposure by personal sampling twice in 1 year, and measured in these PM 2.5 samples the concentration of the soluble transition metals vanadium, chromium, iron, nickel, copper, and platinum. Collected lymphocytes and 24-hour urine samples were analyzed for DNA damage in terms of 7-hydro-8-oxo-2V -deoxyguanosine (8-oxodG). We found that the 8-oxodG concentration in lymphocytes was significantly associated with the vanadi- um and chromium concentrations with a 1.9% increase in 8-oxodG per 1 Mg/L increase in the vanadium concentration and a 2.2% increase in 8-oxodG per 1 Mg/L increase in the chromium concentration. We have previously reported that in this study population the personal exposure to PM 2.5 was associated with an increase in 8-oxodG in lymphocytes. However, vanadium and chromium were associated with the 8-oxodG concentration in lymphocytes independently of the PM 2.5 mass concentration. The four other transition metals were not associated with 8-oxodG in lymphocytes and none of the transition metals was significantly associated with 8-oxodG in urine. Our results could indicate that vanadium and chromium present in PM 2.5 have an effect on oxidative DNA damage that is independent of particle mass and/or other possible toxic compounds contained within this particulate mix- ture. (Cancer Epidemiol Biomarkers Prev 2005;14(5):1340 – 3) Introduction Epidemiologic studies have found exposure to high concen- trations of ambient particulate matter (PM) to be associated with an increase in cancer, especially lung cancer (1, 2). Particles generated by combustion usually consist of a carbon core to which complex mixtures of compounds, such as transition metals, polyaromatic hydrocarbons, and endotoxins, adhere. One of the proposed mechanisms to the observed adverse health effects is that PM can induce oxidative stress mediated by transition metals on the particle surface, by a PM- induced inflammation causing phagocytes to release reactive oxygen species (ROS), and/or by quinones in the particles that produce ROS through redox cycling. Different PM fractions have been found to generate ROS. Soluble transition metals are abundant in the water-soluble PM fraction and in vitro studies have shown that this fraction is able to induce ROS, specifically hydroxyl radicals, through the metal-dependent Fenton reaction both in cell- free systems and biological systems (3-5). In the Fenton reaction, hydroxyl radicals are generated through a transi- tion metal – mediated reduction of hydrogen peroxide. Studies have shown that particle suspensions from which the soluble fraction has been removed also can generate ROS, suggesting that other fractions of PM than the transition metals can induce oxidative stress (5, 6). A biomarker often used in assessing oxidative damage is 7-hydro-8-oxo-2V -deoxyguanosine (8-oxodG), a C8 hydroxyl- ation of guanine, which is believed to be a major product of hydroxyl radical attack on DNA (7). Several experimental studies have found increased concentration of 8-oxodG following exposure to transition metals and PM both in vitro (4, 8, 9) and in vivo (10). PM-related induction of 8-oxodG has been shown to correlate significantly with induction of lung tumors in mice, suggesting that 8-oxodG could be a premuta- genic lesion in PM-induced lung cancer (11). We have previously measured the personal exposure to PM 2.5 (mass of PM with an aerodynamic diameter <2.5 Am) in 49 persons four times during 1 year, and found that personal PM 2.5 exposure was associated with the 8-oxodG concentrations in lymphocyte DNA with an 11% increase in 8-oxodG per 10 Ag/m 3 increase in personal PM 2.5 exposure (12). The aim of this study was to examine the relationship between the personal exposure to water-soluble transition metals in PM 2.5 and oxidative DNA damage. In 49 students from central Copenhagen, we collected personal PM 2.5 exposure twice in 1 year and measured the concentration of soluble transition metals in the PM 2.5 . Collected lymphocytes and urine samples were analyzed for 8-oxodG. Materials and Methods Experimental Design. The personal exposure to PM 2.5 was measured twice, once during summer and once during autumn, in 49 students. Measurements were conducted over 2-weekday periods for each subject as previously described (13). All participants were nonsmokers, living and studying in central Copenhagen. They were 20 to 33 years of age, Received 12/8/04; revised 2/1/05; accepted 3/10/05. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Requests for reprints: Steffen Loft, Institute of Public Health, c/o Department of Pharmacology, The Panum Institute, 18-5-32, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. Phone: 45-35327649; Fax: 45-35327610. E-mail: s.loft@pubhealth.ku.dk Copyright D 2005 American Association for Cancer Research. Cancer Epidemiology, Biomarkers & Prevention 1340 Cancer Epidemiol Biomarkers Prev 2005;14(5). May 2005 on May 29, 2020. © 2005 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from