Regulation of cytochrome P-450. Immunochemical quantitation of eight isozymes in liver microsomes of rats treated with polybrominated biphenyl congeners

• Published in: The Journal of biological chemistry Vol. 258; no. 2; pp. 1282 - 1288
• Main Authors: Dannan, G A, Guengerich, F P, Kaminsky, L S, Aust, S D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25-01-1983; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Antibody Specificity; Biphenyl Compounds - pharmacology; Cytochrome P-450 Enzyme System - immunology; Cytochrome P-450 Enzyme System - metabolism; Endopeptidases - metabolism; Epoxide Hydrolases - metabolism; Immunoelectrophoresis; Isoenzymes - immunology; Isoenzymes - metabolism; Male; Microsomes, Liver - enzymology; Polybrominated Biphenyls - pharmacology; Rats; Rats, Inbred Strains; Serine Endopeptidases
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)33190-9

Specific immunochemical techniques were used to quantitate the levels of eight isozymes of cytochrome P-450 (P-450) and epoxide hydrolase in liver microsomes of untreated rats and rats treated with phenobarbital, 3-methylcholanthrene, a mixture of these two compounds, nine individual polybrominated biphenyl (PBB) congeners, and a commercial mixture of PBBs. Levels of two 3-methylcholanthrene-inducible P-450s (designated P-450 beta NF-B and P-450 beta NF/ISF-G) varied over two orders of magnitude and were highly correlated. The levels of four phenobarbital-inducible P-450s (designated P-450PB-B, P-450PB-C, P-450PB-D, and P-450PB/PCN-E) were all correlated to each other. The level of one form, P-450UT-A, which was present at substantial levels in untreated rats, was inversely correlated to the levels of P-450 beta NF-B and P-450 beta NF/ISF-G. Among the PBB congeners which were examined, the presence of bromine at carbons o to the biphenyl bridge favored the induction of P-450PB-B, P-450PB-C, P-450PG-D, and P-450PB/PCN-E but did not necessarily eliminate the ability to induce P-450 beta NF-B and P-450 beta NF-ISF-G. PBB congeners with 2,2'-dibromo substitution induced P-450 beta NF-B and P-450 beta NF/ISF-G if one of the biphenyl rings contained bromines at positions 2,3, and 4. The induction of P-450UT-F was found to occur to a small extent with three of the compounds and is not readily explained in terms of structure-activity relationships. Although correlations were found among levels of some of the forms of P-450, several important exceptions were noted in relative levels of the individual enzymes. While the correlative data are useful in predicting induction patterns, all eight forms of P-450 appear to be independently regulated to some extent.