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Distribution and induction sites of phenobarbital- and 3- methylcholanthrene-inducible cytochromes P-450 in murine liver: immunohistochemical localization with monoclonal antibodies

PG Forkert, P Mirehouse-Brown, SS Park and HV Gelboin

Department of Anatomy, Queen's University, Kingston, Ontario, Canada.

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.

Volume 34, Issue 6, pp. 736-743, 12/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




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