Original Contribution ACETALDEHYDE (CH 3 CHO) PRODUCTION IN RODENT LUNG AFTER EXPOSURE TO METAL-RICH PARTICLES MICHAEL C. MADDEN,* MICHAEL J. THOMAS, † and ANDREW J. GHIO* *U.S. EPA, NHEERL, Research Triangle Park, NC, USA and † Wake Forest University, Winston-Salem, NC, USA (Received 7 October 1998; Revised 14 January 1999; Accepted 15 January 1999) Abstract—Epidemiological reports demonstrate an association between increased human morbidity and mortality with exposure to air pollution particulate matter (PM). Metal-catalyzed oxidative stress has been postulated to contribute to lung injury in response to PM exposure. We studied the effects of residual oil fly ash (ROFA), a component of ambient air PM, on the formation of lung carbonyls that are indicators of lipid peroxidation. Rats were instilled intratracheally with ROFA (62.5–1000 g) and underwent lung lavage. Lavage fluid carbonyls were derivatized with 2,4-dinitrophe- nylhydrazine, and measured by high performance liquid chromatography with UV detection. Dose-dependent increases in a peak that eluted with the same retention time as the acetaldehyde (CH 3 CHO) derivative was observed in rats treated with ROFA 15 min after instillation (up to 25-fold greater than saline treated controls). The identification of CH 3 CHO was confirmed using gas chromatography-mass spectroscopy. ROFA-induced increases in other lavage fluid carbonyls were not seen. Increased CH 3 CHO in lavage fluid was observed as late as 8 h later. No increase in CH 3 CHO was observed in plasma from ROFA-treated rats. An increased formation of CH 3 CHO was observed in a human airway epithelial cell line incubated with ROFA suggesting a pulmonary source of CH 3 CHO production. Instillation of solutions of metals (iron, vanadium, nickel) contained in ROFA, or instillation of another ROFA-type particle containing primarily iron, also induced a specific increase in CH 3 CHO. These data support the hypothesis that metals were involved in the increased CH 3 CHO formation. Thus metals on PM may mediate lung responses through induction of lipid peroxidation and carbonyl formation. © 1999 Elsevier Science Inc. Keywords—Oxidants, Metals, Acetaldehyde, Air pollution, Free radicals INTRODUCTION Concentrations of particulate matter in ambient air have been reported to be associated with human mortality and morbidity due to a cardiopulmonary injury [1,2]. Ambi- ent air particles are a complex mixture of components that can vary geographically in terms of major constitu- ents. Metals are almost always present in particles in measurable concentrations [3]. In numerous urban sites, ambient air contains residual oil fly ash (ROFA) that contains high concentrations of soluble transition metal compounds including vanadium, iron, and nickel sul- fates. Instillation of rats with this specific emission source particle produces lung injury that includes an incursion of neutrophils, and increased protein con- centrations in bronchoalveolar lavage fluid [4]. Other biological responses (i.e., prostaglandin and cytokine production) observed after exposure of the lung cells in vitro to ROFA implicate the metal content of this particle and resultant oxidative stress in induction of the responses [5,6]. Transition metals catalyze formation of reactive oxy- gen species that can initiate lipid peroxidation. A byprod- uct of lipid peroxidation are carbonyls derived from membrane lipids [7]. In addition, reactive oxygen spe- cies can react with other biomolecules such as proteins to produce carbonyls [8]. Consequently, carbonyl gen- eration can reflect exposure to an oxidative stress. Furthermore, some carbonyls may participate as me- diators of biological responses to the exposure includ- Address correspondence to: Michael C. Madden, U.S. EPA Human Studies Facility, 104 Mason Farm Road, MD# 58D, Chapel Hill, NC 27599-7315, USA. The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency and approved for publication. Ap- proval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use. Free Radical Biology & Medicine, Vol. 26, Nos. 11/12, pp. 1569 –1577, 1999 Copyright © 1999 Elsevier Science Inc. Printed in the USA. All rights reserved 0891-5849/99/$–see front matter PII S0891-5849(99)00027-1 1569