The binding of benzo(a)pyrene to subcellular structures of rat liver

Abstract

1. 1. The development of the polycyclic aromatic hydrocarbon binding protein in cytosol of rat liver has been studied. The highest amount was observed in the cytosol of the 11 day old rat (60 fmoles/mg protein). Adult levels (20 fmoles/mg protein) were reached at the age of 25 days. The fetal rat liver contains only minute amounts of the binding protein. 2. 2. Benzo(a)pyrene (BP) proved to be an inducer of the binding protein. This induction was age dependent, the highest induction (about 10-fold) being observed in liver of rats older than 30 days. No induction could be observed in the fetal liver, while during the period of high endogenous content of the binding protein, the content of the binding protein was lower after treatment of the rat with BP. A high endogenous amount of binding protein was found to parallel a high degree of induction of cytosolic NAD(P)H dehydrogenase (DT-diaphorase) by BP. 3. 3. The induction of the binding protein proved to be sensitive to SKF-525A. Since SKF-525A does not induce the binding protein, it is concluded that metabolic conversion of BP is required for the induction. 4. 4. BP bound to the 100,000 g supernatant of rat liver was bound to nuclei, nuclear envelopes, and microsomes. The dissociation constant for this binding was found to be 0.3 nM. The highest amount of binding was observed in nuclei isolated from the adult rat liver. Fetal rat liver nuclei demonstrated about 40 × less binding of BP bound to 100,000 g rat liver supernatant than adult rat liver nuclei.