AJP - Cell Physiology, Vol 234, Issue 3 102-C109, Copyright © 1978 by American Physiological Society
Induction of cytochrome P-450 in a selective subpopulation of hepatocytes
J. J. Gumucio, L. J. DeMason, D. L. Miller, S. O. Krezoski and M. Keener
The objective of this study was to determine whether the inductive effect
of phenobarbital (PB) on liver cytochrome P-450 was the result of the
action of this drug on all or some hepatocytes. For this purpose, a light
(cell band I) and a heavy (cell band II) subpopulation of hepatocytes were
separated from rat liver in a continuous density gradient. To determine the
location of these hepatocytes in tissue, [14C]bromobenzene, which binds
covalently to centrilobular hepatocytes, was administered. The specific
activity (14C dpm/mg protein) was greater in cells of band I than in cells
of band II, suggesting a predominant contribution of centrilobular
hepatocytes to the lighter cell band. Microsomes were separated from each
cell subpopulation after 3 days of PB administration and cytochrome P-450
was measured. Although a fivefold increment in cytochrome P-450 content of
light hepatocytes was noted, the content of heavy hepatocytes was similar
to that of the respective subpopulation in controls. Concomitantly, PB
administered for 3 days induced the smooth endoplasmic reticulum of
centrilobular hepatocytes only, as revealed by electron microscopy of whole
tissue. These results indicated that PB induces cytochrome P-450 in a
selective subpopulation of hepatocytes, most likely located near the
terminal hepatic venule.
