| 8-Hydroxy-2´-deoxyguanosine, A Major Mutagenic Oxidative DNA Lesion, and DNA Strand Breaks in Nasal Respiratory Epithelium of Children Exposed to Urban Pollution Lilian Calderón-Garcidueñas,1,2 Lian Wen-Wang,3 Yu-Jing Zhang,3 Antonio Rodriguez-Alcaraz,4 Norma Osnaya,2 Anna Villarreal-Calderón,2 and Regina M. Santella3 1Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
2Instituto Nacional de Pediatria, Mexico City, Mexico
3Division of Environmental Health Sciences, Columbia University, New York, New York, USA
4Soc Mex ORL y CCC, Mexico City, Mexico Abstract
Southwest metropolitan Mexico City children are repeatedly exposed to high levels of a complex mixture of air pollutants, including ozone, particulate matter, aldehydes, metals, and nitrogen oxides. We explored nasal cell 8-hydroxy-2´-deoxyguanosine (8-OHdG) , a major mutagenic lesion producing G T transversion mutations, using an immunohistochemical method, and DNA single strand breaks (ssb) using the single cell gel electrophoresis assay as biomarkers of oxidant exposure. Nasal biopsies from the posterior inferior turbinate were examined in children in grades one through five, including 12 controls from a low-polluted coastal town and 87 Mexico City children. Each biopsy was divided for the 8-OHdG and DNA ssb assays. There was an age-dependent increase in the percentage of nasal cells with DNA tails > 10 µm in Mexico City children: 19 ± 9% for control cells, and 43 ± 4, 50 ± 16, 56 ± 17, 60 ± 17 and 73 ± 14%, respectively, for first through fifth graders (p < 0.05) . Nasal ssb were significantly higher in fifth graders than in first graders (p < 0.05) . Higher levels (2.3- to 3-fold) of specific nuclear staining for 8-OHdG were observed in exposed children as compared to controls (p < 0.05) . These results suggest that DNA damage is present in nasal epithelial cells in Mexico City children. Persistent oxidative DNA damage may ultimately result in a selective growth of pr eneoplastic nasal initiated cells in this population and the potential for nasal neoplasms may increase with age. The combination of 8-OHdG and DNA ssb should be useful for monitoring oxidative damage in people exposed to polluted atmospheres. Key words: air pollution, biomarker, children, DNA damage, DNA strand breaks, 8-hydroxy-2´-deoxyguanosine, Mexico City, nasal epithelium, oxidative DNA damage, reactive nitrogen species, reactive oxygen species. Environ Health Perspect 107:469-474 (1999) . [Online 4 May 1999] http://ehpnet1.niehs.nih.gov/docs/1999/107p469-474 calderon-garciduenas/abstract.html Address correspondence to L. Calderón-Garcidueñas, MD #58D, U.S. EPA, Research Triangle Park, NC 27711 USA. Telephone: (919) 966-0675. Fax: (919) 966-6271. E-mail: calderon.lilian@epamail.epa.gov Special thanks to A. Carnevale, (Instituto Nacional de Pediatria, Mexico City) for her constant support and encouragement. The authors are indebted to C. Lawler (University of North Carolina at Chapel Hill) for her statistical advice and to J. Villarreal-Calderón for the control population clinical assistance. This study was supported in part by NIEHS training grant T32 ES07126, NIH ES05116, CA 73330, ES09089, and CD902908. Received 5 June 1998 ; accepted 5 November 1998.
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