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.

Diet, metabolic polymorphisms and dna adducts: The epic‐Italy cross‐sectional study

“…A similar seasonal variation had also been reported among lung cancer cases (Tang et al, 1995). Photochemical pollution is increased in periods characterised by high temperatures and high levels of solar radiation in urbanised areas; ozoneactivated chemical compounds could play a role in determining DNA lesions, directly or indirectly by activating other compounds in a complex cascade mechanism (Calderon-Garciduenas et al, 1999). Ozone has also been reported as able to induce an increased permeability of respiratory tract epithelia to chemicals (Brockaert et al, 1999;Bhalla, 1999).…”

Oxidative stress and metal carcinogenesis

“…Considerable evidence shows the increase of 8-OHdG levels in various human cancers [66,67] and in animal tumor models [68]. An 8-OHdG-mediated transversion of G:C to T:A is the most well-known event found in mutated oncogenes and tumor suppressor genes [69]. During DNA replication, the formation of 8-OHdG by the reaction of ROS with dGTP mediates transversion of A:T to C:G [70].…”

Mechanisms of Genotoxicity of Particles and Fibers

“…However, their relevance in particle and fiber research is more questionable, as particles or fibers are unlikely to reach the bloodstream to some significan t extent, with the exception of organic compounds on "carrier" particles such as diesel exhaust particles and possibly the ultrafine component of PM (Oberdörster, 2001;Nemery et al, 2001). In this regard, it is interesting to notice the tendency to use more appropriate target cells or tissues, such as, buccal smears, sputum cells, or nasal brush cells (Calderon-Garciduenas et al, 1999;. Human data are not the most appropriate to determine particle genotoxicity, but these studies may be highly relevant for hazard identification and identification of susceptible individuals, and also have the main advantage that they do not require extrapolation from animal/experimental dose to human (occupational) exposure.…”