Microsomal metabolism of 4-(N,N-diacetylamino)benzo[a]pyrene: a potent mutagenic arylamide derived from a carcinogenic polycyclic aromatic hydrocarbon.
4-(N,N-Diacetylamino)benzo[a]pyrene, a potent mutagen, is derived from a carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene. Metabolism of this compound by rat liver microsomes was studied. Metabolites were separated by reversed-phase high-performance liquid chromatography and were identified by analysis of their UV-vis absorption, mass, and proton nuclear magnetic resonance spectral data. Seven metabolites were identified, namely, the 9-phenol, 1,9-hydroquinone, and trans-9,10-dihydrodiol of 4-(N,N-diacetylamino)benzo[a]pyrene, 4-(N-acetylamino)benzo[a]pyrene, and the 5-phenol, 5,9-hydroquinone, and trans-9,10-dihydrodiol of 4-(N-acetylamino)benzo[a]pyrene. Comparison of these results with those of metabolism of benzo[a]pyrene indicates that the N,N-diacetylamino substitutent at the 4-carbon of benzo[a]pyrene inhibits metabolism at the peri position (3-carbon) and positions (6-, 7-, and 8-carbons) remote from the substituent. The results also indicate that while 4-(N,N-diacetylamino)-benzo[a]pyrene is a substrate of the rat liver microsomal deacetylase, the formed 4-(N-acetylamino)benzo[a]pyrene apparently is not a substrate.
Chou
M W
MW
National Center for Toxicological Research, Jefferson, Arkansas 92079.
Miller
D W
DW
Freeman
J P
JP
Fu
P P
PP
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001580:Benzopyrenes / Q000302:isolation & purification* / Q000378:metabolism; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D009153:Mutagens / Q000302:isolation & purification*; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry
D001580:Benzopyrenes; D002273:Carcinogens; D009153:Mutagens; D001564:Benzo(a)pyrene; C035240:4-N,N-diacetylaminobenzo(a)pyrene