Environmental Impact on Perinatal Lung Metabolism

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant) This proposal describes a tightly unified effort between metabolomic specialists and environmental health researchers who will collaboratively characterize the development of asthmatic-type respiratory malfunctions in newborn and young adult rats, caused by model airborne particles using (a) soot particles and (b) secondhand smoke or environmental tobacco smoke (ETS). First, the investigators will compare the effects of soot and ETS at a concentration of 1 mg/m3 on the development of respiratory malfunctions in newborn and young adult rats. These effects will be correlated by comparing these model particles with respect to physical parameters and particulate matter composition. Second, the investigators will establish routes of primary metabolization and transport of organic pollutants from pregnant mothers' lungs to blood plasma. Third, the investigators will study metabolic aberrations in fetal, newborn and young adult rat's lungs. By this, links will be established between the type of particulate matter, its organic composition, the timing of metabolic changes in lung development, and the onset and progression of airways dysfunction. This unique combination of biomedical designs with metabolomic assessments will test the hypotheses that (a) perinatal exposure to organic constituents of airborne matter cause alterations in maturation as well as cellular structure and function in the lungs of young adult rats, (b) organic components deposited in the mother 's lung are directly involved in the development of pulmonary diseases such as airway hyper-reactivity, in addition to secondary alterations in immune response or release of bronchoconstrictive mediators by neuroendocrine cells, and (c) the development of respiratory malfunctions are associated with characteristic metabolic changes and can be distinguished from non-specific stress-related changes. Testing of these hypotheses will be enabled by a combination of cutting-edge analytical and metabolomic techniques at a high throughput level. Primary analytical tools will be gas chromatograph (GC)xGC-time of flight (TOF) mass spectrometry (MS) in combination with automatic peak annotation, enabling multivariate statistical comparisons of metabolic changes as well as compositional analysis of airborne model particles. Data will be complemented by full scan liquid chromatography (LC)-ion trap mass spectrometry and unbiased biomarker detection, and multi-target characterization of metabolites as a result of organic pollutants in lung tissues by LC-triple quadrupole MS/MS.