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Alterations of pulmonary benzo[a]pyrene metabolism by reactive oxygen metabolites.
Flowers NL; Miles PR
Toxicology 1991 Jan; 68(3):259-274
The effects of superoxide anion radical and hydrogen-peroxide (7722841) (H2O2) on the metabolism of benzo(a)pyrene (50328) (BP) by rat lung microsomes were examined. Lung microsomes were prepared from male Sprague-Dawley-rats, and incubated with superoxide anion radical or H2O2 for 30 minutes at 0.3, 0.7, 1.0 or 2.8mg/ml microsomal protein, alone or with the addition of superoxide- dismutase (SOD), catalase, sodium-benzoate, mannitol, xanthine, xanthine-oxide, or uric-acid. Exposure of microsomes to superoxide anion radical resulted in a concentration dependent decrease in benzo(a)pyrene-hydroxylase (BP-hydroxylase) activity, up to about 70% inhibition. Addition of SOD restored BP-hydroxylase activity to 88% of control, catalase restored 50% of the control activity, and complete restoration was seen with SOD and catalase together. H2O2 decreased BP-hydroxylase activity in a dose dependent fashion, with maximal inhibition of approximately 40%, and the addition of catalase completely reversed this effect. Super anion radical and H2O2 decreased cytochrome-P-450 content and NADPH-cytochrome-P-450- reductase activity in a concentration dependent manner, and SOD eliminated this effect, while catalase produced a slight reversal of the effects on cytochrome-P-450, but had no effect on the decrease in NADPH-cytochrome-P-450-reductase. The ratio of dihydrodiols and quinones to phenols was increased more than two times after exposure to super oxide radical. The authors conclude that exposure of pulmonary microsomes to oxygen metabolites can result in a slowing of BP metabolism and an increase in the accumulation of potentially toxic metabolites.
NIOSH-Author; Pyrenes; Metabolic-study; Laboratory-animals; Lung-function; Microsomal-enzymes; Oxidative-metabolism; Toxic-effects
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