| The lungs are composed of an architectural framework, conducting airways, and alveolar sacs. To prevent collapse of lung tissue, alveolar type II (AT II) cells produce pulmonary surfactant (PS), an amphipathic material composed mostly of saturated phospholipids and cholesterol that lines the air/water interface. Alterations to lung cells (neoplastic transformation) or the PS system (composition and function) may result in respiratory complications. We studied the biochemical composition of urethane-induced AT II neoplasms, the role of cholesterol in PS function, and the effect of exposure to pulmonary toxins produced by the mold S. chartarum. To assess biochemical alterations of neoplastic mouse lung and excised human lung neoplasms, we used a novel technique called Fourier-transform infrared spectroscopy (FTIR), which provides information based on absorption patterns of molecules. Results showed unique biochemistry of mouse neoplasms compared to normal mouse lung. Analyses of human lung lesions revealed also unique but subtle biochemical differences between neoplasms. To study PS function we used capillary surfactometry (CS), which analyzes the ability of a surface-active material to ensure free airflow, thus simulating the small airways. Results demonstrated that excess cholesterol within PS obtained from healthy and tumor-bearing hypercholesterolemic mice had diminished ability to maintain free airflow. Finally, FTIR analyses of PS from mice exposed to S. chartarum spores demonstrated alterations to PS phospholipids. S. chartarum's epigenetic properties were revealed by through analyses of lung fibroblast DNA fragmentation. Alterations to DNA biochemistry, excess PS cholesterol, and epigenetic properties of S. chartarum spore toxins may contribute to the development of reversible and/or irreversible respiratory disorders and diseases. |
