The objectives of this research are (1) to test the hypothesis that human cells treated in long-term, low-dose assays with complex mixtures of chemicals associated with respirable particles from urban air and combustion sources will achieve a constant low rate of mutation as has been observed in experiments with individual mutagenic compounds, (2) to quantify known human cell mutagens in these samples to better understand the relationship between sample composition and mutation rate, (3) to determine the sources and geographic distribution of human cell mutagens in respirable particle samples collected at five sites at the northeast United States, and (4) to determine the key reaction mechanisms by which mutagens are formed in combustion so as to reduce or avoid their formation. Large-quantity samples (in excess of 20 g) of respirable particles (i.e., those particles < approximately 2-3 microns in diameter) will be collected from urban air and from combustion sources known to contribute to the atmospheric load of human cell mutagens (i.e., wood and cigarette smoke, diesel and gasoline engine exhaust, and natural gas burner exhaust). Whole extracts of these samples, extract fractions enriched in PAH and oxy-PAH, and intact particles will be tested in human cells using the long-term (i.e.,>10 days), low-dose assay protocol. GC-MS analysis will be used to determine the composition of human cell mutagens in these samples. In addition, an ongoing analysis of a set of year-long respirable particle samples collected at five sites in the northeastern US-three sites in Massachusetts and two in western New York-will be completed using bioassay-directed chemical analysis to identify human mutagens that contribute significantly to the total mutagenicity of the samples. The results from the northeastern samples will be compared with those obtained from a similar set of respirable particle samples collected in the Los Angeles basin to determine whether there are significant regional differences in human cell mutagenicity and chemical composition. The contribution of various emission sources to the atmospheric samples will be determined via source/receptor modeling techniques to provide insight as to how the emissions from air pollution led to the observed human cell mutagenicity. Finally, the key intermediates, reaction mechanisms and rates of formation of combustion-generated human mutagens, particularly PAH and oxy-PAH, will be studied in laboratory combustors with the goal of understanding how to reduce or avoid the formation of human mutagens in practical combustors. We have learned as part of this research that emission from natural gas burners account for nearly 50% of the total mutagenicity in atmospheric respirable particles; therefore, particular emphasis will be given to the study of mutagen formation in natural gas combustion reactions.
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