0000000000266506
AUTHOR
B. Deckers-schmelzle
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.
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…