Nuclear uptake and subsequent nuclear metabolism of benzo(a)pyrene complexed to cytosolic proteins.
The binding of [3H]benzo(a)pyrene to proteins of rat liver cytosol, the nuclear uptake of cytosolic protein-bound [3H]-benzo(a)pyrene, and the subsequent nuclear metabolism of the polycyclic hydrocarbon were investigated. The binding of [3H]benzo(a)pyrene to cytosol had a saturable high affinity component with a Kd of 2.54 nM and a capacity of 530 fmol/mg protein. Specific binding of [3H]benzo(a)pyrene to cytosol was also assayed using sucrose density gradient analysis. Nuclear uptake of protein-bound [3H]benzo(a)pyrene was demonstrated both directly and by sucrose density gradient analysis. The nuclear benzo(a)pyrene was readily converted to metabolites which were qualitatively and quantitatively no different from nuclear metabolites of exogenously (not protein associated) added [3H]benzo(a)pyrene.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism* / Q000494:pharmacology; D001711:Biotransformation; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
D001580:Benzopyrenes; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System