Abstract
3,4-Benzpyrene and 3-methylcholalnthrene were injected into rats and at several intervals thereafter the hepatic intracellular distribution of these compounds and their metabolites was determined. The compounds were taken up rapidly by the liver and immediately incorporated into the 600 and 10,000 x g fractions. They were subsequently metabolized and the polar derivatives were transferred to the cytosol fraction. Binding time within the cytosol is apparently short and the metabolites are transported rapidly into the bile and into the blood. Injected metabolites of 3,4-benzpyrene and 3-methylcholanthrene were recovered mainly in the cytosol. Direct addition of 3,4-benzpyrene or 3-methylcholanthrene to liver homogenates resulted in binding to the 600 and 10,000 x g fractions, whereas the metabolites added in vitro were found principally in the cytosol. Thus, the subcellular distribution is dependent upon the physicochemical properties of the compounds rather than upon specific transport systems. Succinylsulfathiazole and ouabain, which are excreted in the bile without prior metabolism, are found primarily within the cytosol at all times after injection. It would appear that transport into the cytosol is a required step prior to biliary excretion. For compounds that are excreted in the bile as metabolites, this transport step is governed by the rate of metabolism. which thereby serves as the rate-limiting process in their biliary excretion.
Footnotes
- Received April 24, 1972.
- Accepted July 17, 1972.
- © 1972 by The Williams & Wilkins Co.