0000000000266505
AUTHOR
E. Klaus
Effect of Monooxygenase Inducers on the Binding of Benzo-(A)Pyrene Metabolites to Cellular Macromolecules in Perfused Rat Lungs
The irreversible binding of metabolically activated [3H]-benzo(a)pyrene (BP) to cellular macromolecules of isolated perfused rat lungs was studied. Lungs from differently pretreated animals were perfused in situ in a recirculating system without ventilation. BP with a specific activity of 10 mCi/μmol was added to 50 ml perfusion medium containing 40% washed bovine erythrocytes to a final concentration of 1 μM. DNA, RNA and protein fractions were isolated and assayed for irreversibly bound radioactivity.
Enzymic control of irreversible binding of metabolically activated benzo(a)pyrene in perfused rat liver by monooxygenase activity.
Addition of [3H]-benzo(a)pyrene to the perfusion medium of isolated rat livers results in irreversible binding of radioactivity to DNA, RNA and protein. Binding to DNA accounted for about 0.1% of the total radioactivity which was bound in livers from animals treated with oil or saline and was increased by a factor of 3–5 after pretreatment of the animals with β-naphthoflavone or with phenobarbital. When the inhibitiors of monooygenase activity, α-naphthoflavone or metyrapone, were present in the perfusion medium, irreversible binding was reduced in livers from both β-naphthoflavone- and phenobarbital-pretreated animals, irrespective of the inhibitor used.
Binding of benzo(a)pyrene metabolites to cellular DNA in perfused rat lungs
The influence of pretreatment with monooxygenase inducers on total irreversible binding of metabolically activated [3H]-benzo(a)pyrene to cellular DNA and the formation of benzo(a)pyrene metabolite-deoxyribonucleoside adducts after cytochrome P-448 induction was studied in perfused rat lungs. Pretreatment with the cytochrome P-448 inducer beta-naphthoflavone increasing binding by a factor of 23. In lungs of induced animals, 0.45 pmoles of benzo(a)pyrene equivalents were bound per mg DNA. Binding to RNA and to protein was also considerably induced by beta-naphthoflavone. Phenobarbital treatment did not significantly increase binding to cellular macromolecules of rat lung. Analysis of hydroly…
Ethoxyquin feeding to rats increases liver microsome-catalyzed formation of benzo(a)pyrene diol epoxide--DNA adduct.
Abstract The ability of rat liver microsomes to catalyze the formation of benzo(a)pyrene 7,8-diol-9,10-epoxide — DNA nucleoside adduct was increased threefold by feeding 0.5% ethoxyquin to the animals. Microsomal epoxide hydratase activity was enhanced i parallel by a factor of 3 while aryl hydrocarbon hydroxylase activity was not induced. Liver microsomes from rat pretreated with 3-methylcholanthrene produced an increased proportion of diol epoxide — DNA adduct when ethoxyquin had been fed to the animals. The main chromatographic peak formed by microsomes from 3-methylcholanthrene treated rats which contains DNA adducts of secondary benzo(a)pyrene phenol metabolites is reduced when the ani…
Similar level of metabolic activation of benzo(a)pyrene in perfused rat lung and liver and protection of lung by liver in a combined perfusion system
Abstract Irreversible binding of metabolically activated benzo(a)pyrene to DNA, RNA and protein proceeds by a different time course in perfused liver and lung of 5,6-benzoflavone-treated rats. Peak binding in liver is obtained after 15 min while binding in lung continuously increases over 120 min. Total irreversible binding per mg DNA or RNA is in the same order of magnitude in both organs. While binding in lung is lower at 15 min it exceeds binding in liver at 120 min. Binding per mg protein is higher in lung than in liver over the whole perfusion period. Introduction of a liver into the lung perfusion circuit decreases binding in lung. This protection effect is more pronounced when the li…