Alterations in the pulmonary microsomal cytochrome P-450 system after exposure of rats to silica.
Miles-PR; Bowman-L; Miller-MR
Am J Respir Cell Mol Biol 1993 Jun; 8(6):597-604
Male Sprague-Dawley-rats were intratracheally instilled with silica (14808607) in a study of its effects upon the pulmonary microsomal cytochrome-P-450 system. Two weeks after exposure, the test and control animals were sacrificed and the heart and lungs were removed. The lungs and trachea were weighed, then analyzed by alveolar lavage for the presence of surfactant phospholipids. Homogenates of the remaining pulmonary tissue was used to obtain microsomal fractions. From this tissue, measurements were made to determine the levels of all cytochrome-P-450 isozymes, the activity of NADPH/cytochrome-P-450-reductase, and the metabolism of 7- ethoxycoumarin-O-deethylase (7-EC) and 7-ethoxyresorufin-O- deethylase (7-ER) by Western blot analysis, spectrophotometry, and fluorescence spectrophotometry, respectively. Treated rats were found to have lung tissue almost two times heavier than that of untreated animals. In addition, total microsomal protein content in treated animals was nearly five times more concentrated than control animals. Lung microsomal concentrations of several components of the cytochrome-P-450 system were reduced by almost 50% in the lungs of treated animals. Despite this, the overall total of microsomal protein in the lungs was 1.5 to 2.5 half times greater in treated animals. The authors conclude that respiratory silica exposure in rats causes increases in the total lung content of microsomal protein, cytochrome-P-450 and NADPH cytochrome-P-450-reductase, and in 7-EC and 7-ER activity. Also, levels of cytochrome-P-4501A1 seem to be preferentially increased upon exposure to silica.
NIOSH-Author; Enzyme-activity; Laboratory-animals; Silica-dusts; Pulmonary-function; Enzymatic-effects; Respiratory-irritants; Respiratory-system-disorders
Philip R. Miles, Ph.D., Physiology Section, DRDS, NIOSH, 944 Chestnut Ridge Rd., Morgantown, WV 26505
American Journal of Respiratory Cell and Molecular Biology