Antibody inhibition of oxidative activation and inactivation of the carcinogen 2-acetylaminofluorene by purified hepatic cytochrome P-450 from 3-methylcholanthrene pretreated rats.
Immunochemical studies on metabolic N- and ring hydroxylation of 2-acetylaminofluorene (AAF) were performed with total cytochrome P-450 isozymes and with highly purified P-450 D isozyme isolated from liver microsomes from 3-methylcholanthrene (MC)-pretreated rats. In a reconstituted system with rat P-450 D, addition of antibodies against beta-naphthoflavone (BNF) induced rat P-450 B at 15 mg IgG/nmol P-450 inhibited both oxidations completely. With total P-450 isozymes in a reconstituted system, antibody against BNF-rat-P-450 B at 20 mg IgG/nmol P-450 inhibited both oxidations up to 70-80% only. At these concentrations, preimmune antibody or phenobarbital (PB) induced antibody against rat-P-450 B showed no inhibition of AAF oxidations. These results suggest that P-450 D is the predominant cytochrome P-450 isozyme responsible for AAF N- and ring-oxidations in liver microsomes from MC-pretreated rats. Other P-450 isozymes are also suggested to be involved in AAF oxidations.
D015073:2-Acetylaminofluorene / Q000378:metabolism*; D000818:Animals; D000906:Antibodies; D000936:Antigen-Antibody Complex; D001711:Biotransformation; D065607:Cytochrome P-450 Enzyme Inhibitors; D006900:Hydroxylation; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D000906:Antibodies; D000936:Antigen-Antibody Complex; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D008748:Methylcholanthrene; D015073:2-Acetylaminofluorene; D009251:NADPH-Ferrihemoprotein Reductase