RESUMO
Exposure to urban air pollution is linked to increased mortality from cardiopulmonary causes. Urban areas juxtapose large numbers of residences and workplaces with near-road environments, exacerbating traffic-related air pollution (TRAP) exposure. TRAP is the primary source of variability in intraurban air quality, but continuous regulatory monitoring stations lack the spatial resolution to detect fine-scale pollutant patterns that recent studies using long-term, resource-intensive mobile measurements have established as persistent and associated with higher risk of cardiovascular events. This work evaluates a low-cost, fixed-site approach to characterizinglong-term, hyperlocal exposure to oxides of nitrogen (including NO 2 , a common surrogate for TRAP) as part of Green Heart Louisville, a prospective cohort study examining linkages between urban vegetation, local air quality, and cardiovascular health. We used a fixed 60-site network of Ogawa passive samplers in a 12 km 2 section of Louisville, KY, to measure two-week integrated NO 2 , NO x (NO + NO 2 ), and O 3 mixing ratios nominally every two months between May 2018-March 2021. Seasonal NO x averages were 2.5-fold higher during winter than in summer, and annual average NO (calculated by difference in NO x and NO 2 ) and NO 2 ranged from 4-21 ppb and 5-12 ppb, respectively. NO increased 3-to-5-fold within 150 m of highways or major arterial roads and 2-to-3-fold near parking lots. While both NO and NO 2 were elevated in near-road environments, the corresponding O 3 was depressed, consistent with titration by NO. We developed land-use regression models for annual average NO, NO 2 , and NO x using parameters of proximity (distance to nearest road type, restaurant, traffic signal), cumulative occurrence (length of roads, number of restaurants and traffic lights, all in buffers of up to 500 m in 50-m increments), and greenness (normalized difference vegetative index (NDVI)). Adjusted spatial variability explained by the models were 70% (p<0.05), 67% (p<0.05), and 75% (p<0.01) for NO, NO 2 , and NO x , respectively. Common predictors were distances to the nearest restaurant and road as well as total length of roads within 350 m. Only one greenness metric was significant: mean NDVI within 50 m was negatively associated (p=0.02) with NO 2 . We plan to use these hyperlocal models to estimate residential-level exposures of the clinical study participants.
RESUMO
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a genotoxic carcinogen found in tobacco and tobacco smoke. Several in vitro and in vivo assays have been used for evaluating the genotoxicity of tobacco smoke and tobacco smoke constituents like NNK, yet it is not clear which in vitro assays are most appropriate for extrapolating the in vitro responses of these test agents to animal models and humans. The Pig-a gene mutation assay can be performed in vitro, in laboratory animals, and in humans, a potential benefit in estimating in vivo responses from in vitro data. In the current study we used Pig-a as a reporter of gene mutation both in vitro, in L5178Y/Tk+/- cells, and in vivo, in Sprague-Dawley rats. NNK significantly increased Pig-a mutant frequency in L5178Y/Tk+/- cells, but only at concentrations of 100 µg/ml and greater, and only in the presence of S9 activation. Pig-a mutations in L5178Y/Tk+/- cells were detected in 80% of the NNK-induced mutants, with the predominate mutation being GâA transition; vehicle control mutants contained deletions. In the in vivo study, rats were exposed to NNK daily for 90 days by inhalation, a common route of exposure to NNK for humans. Although elevated mutant frequencies were detected, these responses were not clearly associated with NNK exposure, so that overall, the in vivo Pig-a assays were negative. Thus, while NNK induces mutations in the in vitro Pig-a assay, the in vivo Pig-a assay has limited ability to detect NNK mutagenicity under conditions relevant to NNK exposure in smokers.
