Research Reports

This report describes a study by Dr. Jeffrey and colleagues to investigate the potential genotoxicity of components of diesel engine emissions using a variety of biological systems. In the first set of in vitro experiments, radiolabeled nitropyrenes were administered to DNA isolated from human bronchial tissue, mouse embryo fibroblasts, and rabbit tracheal tissue, and elution times were compared by high-pressure liquid chromatography. Antisera antibodies were also prepared against DNA modified by 1-nitrosopyrene to test for the presence of DNA adducts.

This report describes a study by Dr. Beland to investigate the extents to which 1-nitropyrene and 1,6-dinitropyrene, two PAHs found in diesel exhaust, bind DNA in order to better understand the higher relative mutagenicity of 1,6-Dinitropyrene. DNA binding was determined in rats by assay of tissue isolated from a variety of organs. A subset of rats was pretreated with 1-nitropyrene to determine any effect on induction of nitroreductases and subsequent DNA binding by both nitropyrenes.

This report describes a study by Dr. Mauderly and colleagues to examine the influence of preexisting pulmonary emphysema on adverse health effects induced by chronic exposure of rats to diesel engine exhaust (DEE) or NO₂. Rats were exposed 7 hours/day, 5 days/week for 24 months to 9.5 ppm NO₂ or 3.5 mg soot/m³ DEE. Prior to exposure, a subset of rats was instilled with the proteolytic enzyme elastase to induce pulmonary emphysema.

This report describes a study by Dr. Evans and colleagues to develop an early marker of lung injury that changes in response to exposure to NO₂, which is an important component of mobile source emissions. Rats were exposed to NO₂ in concentrations ranging from 0.5 to 30 ppm for 6 hours per day for periods ranging from 2 days to 4 weeks. Urine and bronchoalveloar lavage samples were collected and analyzed for the presence of the lung injury markers hydroxylysin, angiotensin-converting enzyme, and desmosine.

This report describes a study by Dr. Heinrich and colleagues to investigate the effects of exposure to NO₂ and SO₂ or diesel engine exhaust on tumor formation in hamsters. Hamsters were exposed for 6, 10.5, 15, or 18 months to whole diesel exhaust, diesel exhaust without particles, or a mixture of NO₂ and SO₂. Additional groups of animals exposed to each test atmosphere were also injected with 3 or 6 mg of diethylnitrosamine/kg body weight to evaluate any enhancing effect of diethylnitrosamine on exposure-related changes.

This report addressed the hypothesis that hypertrophy of the lung after oxidant injury with ozone or oxygen is due to local generation of lung-specific growth factors. Dr. Tanswell exposed rats to either 85% oxygen, 1 ppm ozone, or air for up to two weeks while samples of plasma, lung washings, and lung tissue were periodically collected. These samples were tested for their effect on the DNA synthesis of purified populations of three major lung cell types (pneumocyte, fibroblast, and endothelial cell) in culture.

This report examined the interactive effects induced by exposure to altitude and carbon monoxide. Dr. Horvath and colleagues exposed 23 healthy young human volunteers living at sea level to concentrations of 0, 50, 100, or 150 ppm carbon monoxide in a hyperbaric chamber simulating altitudes of 55, 1,524, 2,134, or 3, 048 meters above sea level. Maximal aerobic capacity tests were performed under each exposure condition while respiratory and cardiac variables and blood levels of carboxyhemoglobin, hemoglobin, and lactate were monitored.

This report assessed in rats the carcinogenicity of inhaled 1-nitropyrene, a compound frequently adsorbed to diesel particulate matter, and whether this effect is modified when 1-nitropyrene is associated with particles or irritant gases. Dr. Wolff and colleagues exposed rats to atmospheres containing 14C radiolabeled 1-nitropyrene alone or in combination with gallium oxide, sulfur dioxide, or both. After exposure, tissue samples were analyzed for radiolabel content to determine the tissue distribution of 1-nitropyrene and its metabolites.

This report describes a study by Dr. Maher and colleagues to investigate the biological effects of nitropyrene compounds, found in diesel emission particulate, on diploid human fibroblasts in culture in order to better evaluate potential health effects. Diploid human fibroblasts from normal individuals and individuals with a genetic predisposition to cancer were studied and compared through a series of experiments.

This report addressed the hypothesis that exposure to oxidant air pollutants enhances susceptibility to viral infection. Drs. Kulle and Clements exposed healthy human volunteers who were seronegative to cold-adapted influenza A virus to clean air or nitrogen dioxide concentrations of 1, 2, or 3 ppm for two hours a day for three consecutive days. Live influenza A virus was administered intranasally to all participants after the second day of exposure.

This report describes a study by Dr. Crandall and colleagues to investigate the ability of nitrogen dioxide (NO₂) to adversely alter the barrier and transport properties of mammalian alveolar epithelium and cause pulmonary edema. Rat type II alveolar cell monolayers cultured on non-porous and porous surfaces were used as models of isolated alveolar epithelium for in vitro exposure to NO₂.

Addressing the need for better assessment of human exposure to mobile source emissions, this report investigates proteinase inhibitor activity as a potential biomarker of oxidant exposure. In this study by Dr. Johnson, human participants were exposed to 0.5 ppm ozone for four hours on consecutive days and to concentrations ranging from 0.6-2 ppm nitrogen dioxide for three hours. Blood samples were obtained and the functional activity of the proteinase inhibitors, alpha-1-proteinase, and bronchial leukocyte proteinase was assessed.