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ToxSci Advance Access published online on June 16, 2004

Toxicological Sciences, doi:10.1093/toxsci/kfh199
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received January 19, 2004
Accepted June 7, 2004

Respiratory Toxicology

Inherent Redox Properties of Diesel Exhaust Particles: Catalysis of the Generation of Reactive Oxygen Species by Biological Reductants

Chuan-Ju G. Pan 1, Debra A. Schmitz 2, Arthur K. Cho 1, John Froines 3, Jon M. Fukuto 4*

1 Department of Pharmacology, UCLA School of Medicine, Center for the Health Sciences, Los Angeles, CA 90095-1735
2 Department of Environmental Health Sciences, UCLA School of Public Health, Los Angeles, CA 90095-1772
3 Department of Environmental Heath Sciences, UCLA School of Public Health, Los Angeles, CA 90095-1772; UCLA Interdepartmental Program in Molecular Toxicology, Center for the Health Sciences, Los Angeles, CA 90095-1772
4 Department of Pharmacology, UCLA School of Medicine, Center for the Health Sciences, Los Angeles, CA 90095-1735; UCLA Interdepartmental Program in Molecular Toxicology, Center for the Health Sciences, Los Angeles, CA 90095-1772

* To whom correspondence should be addressed. E-mail: jfukuto{at}mednet.ucla.edu.


   Abstract

The toxicity of diesel exhaust particles (DEP) can be due to the particle itself, extractable components or both. Many studies focus on the biological properties of DEP-extractable components although it is possible that chemical properties inherent to the DEP itself can lead to toxicity. Thus, an examination of the chemistry inherent to DEP was carried out. Herein, we report that DEP are capable of catalyzing the consumption of O2 (monitored using a Clarke electrode) by ascorbate and thiols leading to the generation of reactive oxygen species. Consistent with the idea that DEP are capable of catalyzing the generation of reactive oxygen species, they were also found to catalyze DNA strand breakage via an O2- and reductant-dependent process. Significantly, extraction of DEP with either organic solvent (methylene chloride) or acid (aqueous HCl) did little to abrogate this chemistry. Finally, using electron paramagnetic spectrometry (EPR), DEP were found to have paramagnetic properties. The paramagnetic character of DEP may be important to their ability to catalyze the formation of reactive oxygen species and at least partially responsible for their toxicity. These findings indicate that studies that primarily consider or examine particle extracts as the toxic components of DEP may be insufficient in describing the toxicity associated with DEP exposure.

Keywords: Diesel exhaust particles, DNA cleavage, free radical, oxidative stress
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