title: 8-hydroxy-2'-deoxyguanosine, a major mutagenic oxidative DNA lesion, and DNA strand breaks in nasal respiratory epithelium of children exposed to urban pollution.
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 microm 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.
authors.affiliation: Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. calderon.lilian@epamial.epa.gov
authors.forename: L
authors.initials: L
authors.lastname: Calderón-Garcidueñas
authors.forename: L
authors.initials: L
authors.lastname: Wen-Wang
authors.forename: Y J
authors.initials: YJ
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Rodriguez-Alcaraz
authors.forename: N
authors.initials: N
authors.lastname: Osnaya
authors.forename: A
authors.initials: A
authors.lastname: Villarreal-Calderón
authors.forename: R M
authors.initials: RM
authors.lastname: Santella
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D002470:Cell Survival; D002648:Child; D004247:DNA / Q000032:analysis* / Q000187:drug effects; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D004787:Environmental Pollution / Q000009:adverse effects*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008800:Mexico; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics*; D014505:Urban Population
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine