Pulmonary microsomal metabolism of benzo(a)pyrene following exposure of rats to silica.
Miles-PR; Ma-JYC; Bowman-L; Miller-MR
J Toxicol Environ Health, A 1996 Jul; 48(5):501-514
The effects of administering silica (14808607) to rats on the pulmonary microsomal metabolism of benzo(a)pyrene (50328) (BP) was examined. Male Sprague-Dawley-rats were exposed to 25 milligrams of silica by intratracheal instillation. Two weeks later, lung microsomes were obtained and the amounts of microsomal tissue and metabolites formed during the in-vitro microsomal metabolism of BP were measured. Production of BP metabolites was linear for 30 minutes; hydroxylated metabolites were produced 50% less in silica treated rats. The amount of BP-4,5-diol was reduced 60%, 3-hydroxy- BP was reduced 70%, and BP-9,10-diol was reduced 45% by silica. The amount of three BP quinones were not altered. The metabolism of BP was modified in a differential manner, suggesting an increase in the potential for accumulation of more toxic forms. Following exposure to silica, the potential existed for total lung production of increased amounts of some BP metabolites, especially BP-7,8-diol and BP quinones. The authors conclude that exposure of rats to silica affects the ability of the lungs to metabolize BP, which may be important in the link between silicosis and lung cancer.
NIOSH-Author; Pyrenes; Laboratory-animals; Silicates; Lung-cancer; Microsomal-enzymes; Lung-disorders; Lung-irritants; Carcinogens; Mineral-dusts
Philip R. Miles, PhD, Physiology Section, DRDS, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505, USA
Journal of Toxicology and Environmental Health, Part A: Current Issues