Soluble metals as well as the insoluble particle fraction are involved in cellular DNA damage induced by particulate matter

Molecular and Cellular Biochemistry - Tập 234 - Trang 317-326 - 2002
Ad M. Knaapen1, Tingming Shi1, Paul J.A. Borm1, Roel P.F. Schins1
1Particle Research Core, Research Institute for Environmental Health (IUF), Düsseldorf, Germany

Tóm tắt

Exposure to ambient particulate matter has been reported to be associated with increased rates of lung cancer. Previously we showed that total suspended particulate matter (PM) induces oxidative DNA damage in epithelial lung cells. The aim of the present study was to further investigate the mechanism of PM-induced DNA damage, in which soluble iron-mediated hydroxyl radical (•OH) formation is thought to play a crucial role. Using electron spin resonance (ESR) we showed that PM suspensions as well as their particle-free, water-soluble fractions can generate •OH in the presence of hydrogen peroxide (H2O2), an effect which was abrogated by both deferoxamine and catalase. In addition, PM was also found to induce the •OH-specific DNA lesion 8-hydroxydeoxyguanosine (8-OHdG) in the presence of H2O2 as assessed by dot-blot analysis of calf thymus DNA using an 8-OHdG antibody. In human alveolar epithelial cells (A549), both PM suspensions and the particle-free soluble fraction elicited formation of DNA strand breaks (comet-assay). Unlike the acellular DNA assays, in epithelial cells the DNA-damaging capacity of the particle suspensions appeared to be stronger than that of their corresponding particle-free filtrates. In conclusion, our findings demonstrate that the water-soluble fraction of PM elicits DNA damage via transition metal-dependent •OH formation, implicating an important role of H2O2. Moreover, our data indicate that direct 'particle' effects contribute to the genotoxic hazard of ambient particulate matter in lung target cells.

Tài liệu tham khảo

Pope CA, Bates DV, Raizenne ME: Health effects of particulate airpollution: Time for reassessment? Environ Health Perspect 103: 472–480, 1995 Dockery DW, Pope CA III, Xu X, Spengler JD, Ware JH, Fay ME, Ferris BG, Speizer FE: An association between air pollution and mortality in six U.S. cities. New Eng J Medicine 329: 1753–1759, 1993 Cohen AJ, Pope CA III: Lung cancer and air pollution. Environ Health Perspect 103(suppl 8): 219–224, 1995 Hornberg C, Maciuleviciute L, Seemayer NH: Sister chromatid exchanges in rodent tracheal epithelium exposed in vitro to environmental pollutants. Toxicol Lett 88: 45–53, 1996 Seemayer NH, Hornberg C, Hadnagy W: Comparative genotoxicity testing of airborne particulates using rodent tracheal epithelial cells and human lymphocytes in vitro. Toxicol Lett 72: 95–103, 1994 Hsiao WLW, Mo ZY, Fang M, Shi XM, Wang F: Cytotoxicity of PM2.5 and PM2.5–10 ambient air pollutants assessed by the MTT and the Comet assays. Mutat Res 471: 45–55, 2000 IARC Monograph on the Evaluation of Carcinogenic Risk to Humans, vol 49: Chromium, Nickel and Welding. IARC, Lyon, France, 1990 Donaldson K, MacNee W: Potential mechanisms of adverse pulmonary and cardiovascular effects of particulate air pollution (PM10). Int J Hyg Environ Health 203: 411–415, 2001 Gilmour PS, Brown DM, Lindsday TG, Beswick PH, MacNee W, Donaldson K: Adverse health effects of PM10 particles: Involvement of iron in generation of hydroxyl radical. Occup Environ Med 53: 817–822, 1996 Li XY, Gilmour PS, Donaldson K, MacNee W: In vivo and in vitro proinflammatory effects of particulate air pollution (PM10). Environ Health Perspect 105(suppl 5): 1279–1283, 1997 Prahalad AK, Soukup JM, Inmon J, Willis R, Ghio AJ, Becker S, Gallagher JE: Ambient air particles: Effects on cellular oxidant radical generation in relation to particulate elemental chemistry. Toxicol Appl Pharmacol 158: 81–91, 1999 Knaapen AM, Schins RPF, Steinfartz Y, Höhr D, Dunemann L, Borm PJA: Ambient particulate matter induces oxidative DNA damage in lung epithelial cells. Inhal Toxicol 12(suppl 3): 125–132, 2000 Dellinger B, Pryor WA, Cueto R, Squadrito GL, Hegde V, Deutsch WA: Role of free radicals in the toxicity of airborne fine particulate matter. Chem Res Toxicol 14: 1371–1377, 2001 Prahalad, AK, Inmon J, Dailey LA, Madden MC, Ghio AJ, Gallagher JE: Air pollution particles mediated oxidative DNA base damage in a cell free system and in human airway epithelial cells in relation to particulate metal content and bioreactivity. Chem Res Toxicol 14: 879–887, 2001 Pryor WA: Why is the hydroxyl radical the only radical that commonly adds to DNA? Free Radic Biol Med 4: 219–223, 1988 Halliwell B, Gutteridge JM: Free radicals in biology and medicine, 2nd edn. Clarendon Press, Oxford, 1989 Lloyd RV, Hanna PM, Mason RP: The origin of the hydroxyl radical oxygen in the fenton reaction. Free Radic Biol Med 22: 885–888, 1997 Harrison RM, Yin J: Particulate matter in the atmosphere: Which particle properties are important for its effects on health. Sci Total Environ 249: 85, 101, 2000 Lloyd DR, Carmichael PL, Phillips DH: Comparison of the formation of 8-hydroxy-2′-deoxyguanosine and single-and double-strand breaks in DNA mediated by fenton reactions. Chem Res Toxicol 11: 420–427, 1998 Toyokuni S, Sagripanti JL: Association between 8-hydroxy-2′-deoxyguanosine formation and DNA strand breaks mediated by copper and iron. Free Radic Biol Med 20: 859–864, 1996 Prahalad AK, Inmon J, Ghio AJ, Gallagher JE: Enhancement of 2′-deoxyguanosine hydroxylation and DNA damage by coal and oil fly ash in relation to particulate metal content and availability. Chem Res Toxicol 13: 1011–1019, 2000 Van Maanen JMS, Borm PJA, Knaapen AM, van Herwijnen M, Schilderman PAEL, Smith KR, Aust AE, Tomatis M, Fubini B: In vitro effects of coal fly ashes: Hydroxyl radical generation, iron release, and DNA damage and toxicity in rat lung epithelial cells. Inhalation toxicol 11: 1123–1141, 1999 Seaton A, MacNee W, Donaldson K, Godden D: Particulate air pollution and acute health effects. The Lancet 345: 176–178, 1995 Donaldson K, Li XY, MacNee W: Ultrafine (nanometre) particle mediated lung injury. J Aerosol Sci 29: 553–560, 1997 Schins RPF: Mechanisms of genotoxicity of particles and fibres. Inhal Toxicol 14: 57–78, 2002 Daniel LN, Mao Y, Saffiotti U: Oxidative DNA damage by crystalline silica. Free Radic Biol Med 14: 463–472, 1993 Don Porto Carero A, Hoet PHM, Verschaeve L, Schoeters G, Nemery B: Genotoxic effects of carbon black particles, diesel exhaust particles, and urban air particulates and their extracts on a human alveolar epithelial cell line (A549) and a human monocytic cell line (THP-1). Environ Mol Mutagen 37: 155–163, 2001 Peters A, Skorkovsky J, Kotesovec F, Brynda J, Spix C, Wichmann HE, Heinrich J: Associations between mortality and air pollution in central Europe. Environ Health Perspect 108: 283–287, 2000 Shi T, Knaapen AM, Begerow J, Birmili W, Borm PJA, Schins RPF: Hydroxyl radical generation and formation of 8-hydroxy-2′-deoxyguanosine by coarse and fine particulate matter. J Aerosol Sci, 2001 (submitted) Musarrat J, Wani AA: Quantitative immunoanalysis of promutagenic 8-hydroxy-2′-deoxyguanosine in oxidized DNA. Carcinogenesis 15: 2037–2043, 1994 Toyokuni S, Tanaka T, Hattori Y, Nishiyama Y, Yoshida A, Uchida K, Hiai H, Ochi H, Osawa T: Quantitative immunohistochemical determination of 8-hydroxy-2′-deoxyguanosine by a monoclonal antibody N45.1: Its application to ferric nitrolotriacetate-induced renal carcinogenesis model. Lab Invest 76: 365–374, 1997 Pick E, Keisari Y: A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture. J Immunol Meth 38: 161–170, 1980 Knaapen AM, Seiler F, Schilderman PAEL, Nehls P, Bruch J, Schins RPF, Borm PJA: Neutrophils cause oxidative DNA damage in alveolar epithelial cells. Free Radic Biol Med 27: 234–240, 1999 Stearns RC, Paulauskis JD, Godleski JJ: Endocytosis of ultrafine particles by A549 cells. Am J Respir Cell Mol Biol 24: 108–115, 2001 Ollikainen T, Puhakka A, Kahlos K, Linnainmaa K, Kinnula VL: Modulation of cell and DNA damage by poly(ADP)ribose polymerase in lung cells exposed to H2O2 or asbestos fibres. Mutat Res 470: 77–84, 2000 Singh NP, McCoy MT, Tice RR, Schneider EL: A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175: 184–191, 1988 Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF: Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35: 206–221, 2000 Collins AR, Ma AG, Duthie SJ: The kinetics of repair of oxidative DNA damage (strand breaks and oxidised pyrimidines) in human cells. Mutat Res 336: 69–77, 1995 Ghio AJ, Stonehuerner J, Daily LA, Carter JD: Metals associated with both the water-soluble and insoluble fractions of an ambient air pollution particle catalyze an oxidative stress. Inhal Toxicol 11: 37–49, 1999 Morel I, Cillard J, Lescoat G, Sergent O, Pasdeloup N, Ocaktan AZ, Abdallah MA, Brissot P, Cillard P: Antioxidant and free radical scavenging activities of the iron chelators pyoverdin and hydroxypyrid-4-ones in iron-loaded hepatocyte cultures: Comparison of their mechanism of protection with that of desferrioxamine. Free Rad Biol Med 13: 499–508, 1992 Henle ES, Linn S: Formation, prevention, and repair of DNA damage by iron/hydrogen peroxide. J Biol Chem 272: 19095–19098, 1997 Piotrowski WJ, Marczak J, Dinsdale D, Kurmanowska Z, Tarasow Y, Komos J, Nowak D: Release of hydrogen peroxide by rat type II pneumocytes in prolonged culture. Toxicol In Vitro 14: 85–93, 2000 Van Klaveren RJ, Roelant C, Boogaerts M, Demedts M, Nemery B: Involvement of an NAD(P)H oxidase-like enzyme in superoxide anion and hydrogen peroxide generation by rat type II cells. Thorax 52: 465–471, 1997 Kinnula VL, Everitt JI, Whorton AR, Crapo JD: Hydrogen peroxide production by alveolar type II cells, alveolar macrophages, and endothelial cells. Am J Physiol 261: L84–L91, 1991 Ye J, Wang S, Leonard SS, Sun Y, Butterworth L, Antonini J, Ding M, Rojanasakul Y, Vallyathan V, Castranova V, Shi X: Role of reactive oxygen species and P53 in chromium(VI)-induced apoptosis. J Biol Chem 274: 34974–34980, 1999 Jimenez LA, Thompson J, Brown DA, Rahman I, Antonicelli F, Duffin R, Drost EM, Hay RT, Donaldson K, MacNee W: Activation of NFkappaB by PM(10) occurs via an iron-mediated mechanism in the absence of IkappaB degradation. Toxicol Appl Pharmacol 166: 101–110, 2000 Shukla A, Timblin C, Berube K, Gordon T, McKinney W, Driscoll K, Vacek P, Mossman BT: Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro. Am J Respir Cell Mol Biol 23: 182–187, 2000 Repine JE, Bast A, Lankhorst I, and The oxidative stress study group: Oxidative stress in chronic obstructive pulmonary disease. Am J Repir Crit Care Med 156: 341–357, 1997 Shi X, Mao Y, Daniel LN, Saffiotti U, Dalal NS, Vallyathan V: Silica radical-induced DNA damage and lipid peroxidation. Environ Health Perspect 102(suppl 10): 149–154, 1994 Park JW, Floyd RA: Lipid peroxidation products mediate the formation of 8-hydroxydeoxyguanosine in DNA. Free Radic Biol Med 12: 245–250, 1992 Perderiset M, Marsh JP, Mossman BT: Activation of protein kinase C by crocidolite asbestos in hamster tracheal epithelial cells. Carcinogenesis 12: 1499–1502, 1991 Gercken G, Berg I, Dorger M, Schluter T: Mechanisms of particle-induced activation of alveolar macrophages. Toxicol Lett 88: 121–129, 1996