A major problem in epidemiology studies is an inability to assess exposures to individual pollutants accurately. Biological markers of exposure to specific pollutants would be invaluable tools for the epidemiologist. Some of the most common environmental pollutants are also the materials that present the most difficult problem as far as development of markers for their exposure. Ozone, NO2, and SO2, for example, can be expected to interact with tissues readily and to be consumed or altered in the process. Certain types of injury may, in themselves, serve as markers of exposure, but most types of injury will not be specific for any one pollutant. The objective of the proposed research is to develop and to validate markers of recent exposures to ambient or reasonable excursions from ambient levels of three airborne pollutants: SO2, NO2, and O3. Characterization of the markers will first be done in animals and, when promising markers have been delineated, validation will be done in samples from humans exposed under well-defined, clinical protocols. While the emphasis in this proposal will be placed on developing markers of recent exposures, the persistence of the markers after exposure will be followed to determine the applicability of the markers for detecting and quantitating more distant exposures. Specific aims to achieve this objective are: 1) To determine chemical markers of exposure to NO2, O3, and SO2. These will include measurement of -S-sulfonates after exposure of rats and dogs to SO2; measurement of aldehydes after ozone exposures of F334/N rats and Beagle dogs; and determination of potential of nitroaromatic residues in proteins as markers of exposure to NO2. 2) To determine biochemical and cytological markers of effect of exposure to NO2, O3, and SO2. These markers will include changes in glycoproteins, extracellular cytoplasmic enzymes, lysosomal and peroxisomal enzymes, arachidonate metabolites, antiproteinases, and total and differential cell counts. 3) To correlate histological changes occurring in nose, upper airways, and lung of rats and dogs following exposure to NO2, O3, and SO2 with biochemical changes. 4) To validate those chemical reaction products and biochemical effects that appear to be reliable markers of exposure to analysis of nasal lavage fluid and sputum from human subjects exposed to known levels of SO2, O3, or NO2.