Characterization of the microsomal cytochrome P-450 species induced in rat liver by 2-acetylaminofluorene.
2-Acetylaminofluorene induces the level of cytochrome P-450 in rat liver microsomes by 50% (p less than 0.001). This induced cytochrome(s) was characterized and compared to the major forms of cytochrome P-450 induced by phenobarbital and 3-methylcholanthrene. The properties investigated were: the absorption maximum of the complex formed between reduced cytochrome P-450 and carbon monoxide; the substrate specificities using aminopyrine, benzphetamine, ethylmorphine, benzo(a)pyrene, ethoxycoumarin, ethoxyresorufin, and 2-acetylaminofluorene itself as substrates; metabolite patterns with benzo(a)pyrene and 2-acetylaminofluorene; sensitivity to different inhibitors; binding spectra with aniline and hexobarbital; and molecular weight as determined by sodium dodecyl sulfate:disc gel electrophoresis. The results indicate that 2-acetylaminofluorene induces a form(s) of cytochrome P-450 especially effective in the metabolism of this substance itself (i.e., the process can be called substrate induction) and different from the major forms of cytochrome P-450 induced by phenobarbital and 3-methylcholanthrene.
D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D001580:Benzopyrenes; D007527:Isoenzymes; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene