Distribution and induction sites of phenobarbital- and 3-methylcholanthrene-inducible cytochromes P-450 in murine liver: immunohistochemical localization with monoclonal antibodies.
Monoclonal antibodies specific for cytochromes P-450 induced by 3-methylcholanthrene (Mab 1-7-1) and phenobarbital (Mab 2-66-3) have been used in an unlabeled peroxidase-antiperoxidase immunohistochemical procedure to investigate the intralobular distribution and induction sites of the hemoproteins within the livers of CD-1, C57BL/6, and DBA/2 mice. 3-Methylcholanthrene-specific cytochromes P-450 were localized predominantly in centrilobular hepatocytes of control mice from all strains and were present at higher levels in CD-1 and C57BL/6 mice than in DBA/2 mice. Treatment with either 3-methylcholanthrene or beta-naphthoflavone produced striking increases of 3-methylcholanthrene-specific cytochromes P-450 in hepatocytes from all regions of the hepatic lobule in CD-1 and C57BL/6 mice, but not in DBA/2 mice. Phenobarbital-specific cytochromes P-450 were localized in hepatocytes throughout all segments of the lobule in control mice, with slightly greater hemoprotein content in centrilobular hepatocytes. Treatment with phenobarbital resulted in enhancement of cytochrome P-450 that was visualized in hepatocytes in all regions of the lobule. Strain-related differences were not observed for phenobarbital-specific cytochromes P-450. These results demonstrate that constitutive levels of 3-methylcholanthrene- and phenobarbital-specific cytochromes P-450 are localized predominantly in centrilobular hepatocytes of murine livers, and induction of the hemoproteins is manifested to the greatest extent in periportal hepatocytes, resulting in a more uniform distribution throughout the hepatic lobule.
Forkert
P G
PG
Department of Anatomy, Queen's University, Kingston, Ontario, Canada.
Mirehouse-Brown
P
P
Park
S S
SS
Gelboin
H V
HV
D000818:Animals; D000911:Antibodies, Monoclonal; D001571:Benzoflavones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000096:biosynthesis; D004789:Enzyme Activation; D000939:Epitopes / Q000032:analysis; D007124:Immunoenzyme Techniques; D008099:Liver / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010634:Phenobarbital / Q000494:pharmacology; D019324:beta-Naphthoflavone
D000911:Antibodies, Monoclonal; D001571:Benzoflavones; D000939:Epitopes; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital