Alterations in pulmonary xenobiotic metabolizing enzyme systems in asbestotic animals.
Rahman-Q; Khan-SG; Ali-S
Proceedings of the VIIth International Pneumoconioses Conference, August 23-26, 1988, Pittsburgh, Pennsylvania, USA. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 90-108, 1990 Nov; (Part II):1330-1335
Changes in pulmonary xenobiotic metabolizing systems induced by asbestos (1332214) were studied in rats. Male albino rats were administered 0 or 5 milligrams chrysotile (12001295) dust intratracheally. Selected rats were killed 1, 4, 8, 16, 90, or 290 days later and the lungs were removed and weighed. Lung cytosol and microsome fractions were prepared. Microsomal cytochrome-P-450 (P450) and glutathione content and benzo(a)pyrene-hydroxylase (BaPOHase) and epoxide-hydratase (EH) activity were determined. The extent of microsomal lipid peroxidation was measured. Cytosolic ascorbic-acid content and glutathione-S-transferase (GST) activity were determined. Lung weights were significantly increased in chrysotile treated rats examined after 90 and 290 days. Chrysotile caused significant decreases in P450 content and BaPOHase and EH activity 1 to 16 days after exposure. The decreases were followed by significant increases at days 90 and 290. GST activity and glutathione content decreased progressively with time, the decreases becoming significant after 90 days. Ascorbic-acid content was significantly decreased 90 and 290 days after chrysotile. Microsomal lipid peroxidation was significantly increased at all time points. The authors conclude that asbestos fibers alter the pulmonary mixed function oxidase system in rats. These changes result in carcinogenic reactive intermediates that are ineffectively cleared being generated, preformed conjugates being hydrolyzed, free radicals being generated, and antioxidants concentrations being decreased. Such changes may favor induction of bronchogenic carcinoma.
In-vivo-studies; Laboratory-animals; Asbestos-fibers; Physiological-chemistry; Lung-tissue; Enzyme-complexes; Biotransformation; Lung-cancer; Lipid-peroxidation
DHHS (NIOSH) Publication No. 90-108
Proceedings of the VIIth International Pneumoconioses Conference, August 23-26, 1988, Pittsburgh, Pennsylvania, USA