Js. Shen et al., IMMUNOHISTOCHEMICAL DEMONSTRATION OF BETA-NAPHTHOFLAVONE-INDUCIBLE CYTOCHROME-P450 1A1 1A2 IN RAT INTRAHEPATIC BILIARY EPITHELIAL-CELLS/, Hepatology, 27(6), 1998, pp. 1483-1491
Although intrahepatic biliary epithelial cells are targets for certain
hepatotoxic chemicals, including some procarcinogens, their ability t
o monooxygenate, and thereby bioactivate and inactivate xenobiotics, r
emains to be established. Thus, the present study was undertaken to im
munohistochemically determine if cytochrome P450 (CYP) 1A1/1A2 is pres
ent and can be induced within these nonparenchymal liver cells. Immuno
peroxidase and immunofluorescent staining for CYP1A1/1A2 was detected
within intrahepatic biliary epithelial cells as well as hepatocytes of
control rats and was markedly enhanced in both cell types by beta-nap
hthoflavone (BNF), Color confocal laser microscopic analyses of dual i
mmunofluorescent staining for CYP1A1/1A2 and cytokeratins 6 and 9 (56
and 64 kd, respectively) provided unequivocal evidence for the presenc
e and induction of CYP1A1/1A2 within intrahepatic bile duct epithelia.
Moreover, microdensitometric analyses of immunoperoxidase staining in
tensities for CYP1A1/1A2 revealed that intrahepatic biliary epithelial
cells of control rats contain 44%, 56%, and 58% as much CYP1A1/1A2 as
do centrilobular, midzonal, and periportal hepatocytes, respectively.
These analyses further revealed that BNF increased the content of CYP
1A1/1A2 in biliary epithelial cells by approximately 120%, while CYP1A
1/1A2 levels in centrilobular, midzonal, and periportal hepatocytes we
re increased by 82%, 159%, and 160%, respectively. The results of this
study represent the first in situ demonstration that mammalian intrah
epatic biliary epithelial cells contain a CYP isoform, and Further tha
t CYP1A1/1A2 can be induced in these cells by BNE These findings there
fore indicate that intrahepatic biliary epithelial cells can oxidative
ly metabolize xenobiotics in situ and that their ability to bioactivat
e and inactivate xenobiotics can be significantly enhanced by CYP1A1/1
A2 induction.