The formation of proximate carcinogens from three polycyclic aromatic compounds by human liver microsomes.
1. The metabolism of 3H-benzo[a]pyrene (BP), 3H-7-methylbenz[c]acridine (7MBAC) and 3H-dibenz[a,j]acridine (DBAJAC) have been studied in human liver microsomes from 13 subjects. 2. When the metabolism of these carcinogens to more polar ethyl acetate-soluble metabolites were compared, the activities towards the nitrogenous carcinogens were twice that determined for BP. 3. The specific rates of formation of the three proximate carcinogens, BP-7,8-dihydrodiol, 7MBAC-3,4-dihydrodiol and DBAJAC-3,4-dihydrodiol per nmol cytochrome P-450 for 12 subjects were positively correlated. 4. These dihydrodiols constituted 5.9 +/- 0.7% (mean +/- SEM), 57.8 +/- 2.6% and 3.0 +/- 0.4% of the total metabolites identified by cochromatography with standards, 7MBAC, DBAJAC and BP respectively.
Sugiyanto
Department of Pharmacy, University of Sydney, NSW, Australia.
Scharping
C E
CE
McManus
M E
ME
Birkett
D J
DJ
Holder
G M
GM
Ryan
A J
AJ
D000166:Acridines / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001564:Benzo(a)pyrene / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010084:Oxidation-Reduction; D011083:Polycyclic Compounds / Q000378:metabolism*
D000166:Acridines; D002273:Carcinogens; D011083:Polycyclic Compounds; C022289:dibenzacridine; C031277:7-methylbenz(c)acridine; D001564:Benzo(a)pyrene; D006899:Mixed Function Oxygenases