Regulation of cytochrome P-450. Immunochemical quantitation of eight isozymes in liver microsomes of rats treated with polybrominated biphenyl congeners.
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.
D000818:Animals; D000918:Antibody Specificity; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism; D007122:Immunoelectrophoresis; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D011075:Polybrominated Biphenyls / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012697:Serine Endopeptidases
D001713:Biphenyl Compounds; D007527:Isoenzymes; D011075:Polybrominated Biphenyls; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases; D010450:Endopeptidases; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase