The nasal cavity is the most common portal of entry to the human body and a well-known target site for a wide range of air pollutants and chemically induced toxicity and carcinogenicity. DNA single-strand breaks (SSB) can be used as a biomarker of oxidant exposure and as an indicator of the carcinogenicity and mutagenicity of a substance. We examined the utility of using the alkaline single cell gel electrophoresis assay (SCGE) for measuring DNA damage in children's nasal epithelium exposed to air pollutants. We studied 148 children, ages 6-12, including 19 control children from a low polluted Pacific port and 129 children from Southwest Metropolitan Mexico City, an urban polluted area with high ozone concentrations year-round. Three sets of two nasal biopsies were taken in a 3-month period. All exposed children had upper respiratory symptoms and DNA damage in their nasal cells. Eleven- and twelve-year-olds had the most DNA damage, and more than 30% of children aged 9-12 exhibited patchy areas of squamous metaplasia over high-flow nasal regions. These areas had the greatest numbers of damaged DNA cells (P < or = 0.001) and a large number of DNA tails > 80 microns (P < 0.001) when compared to the contralateral macroscopically normal site in the same child. The youngest children with significantly less outdoor exposure displayed patchy areas of goblet cell hyperplasia and had the least DNA damage. These findings suggest that SCGE can be used to monitor DNA damage in children's nasal epithelium and, further, the identification of DNA damage in nasal proliferative epithelium could be regarded as a sentinel lesion, most likely due to severe and sustained cell injury.