The formation of proximate carcinogens from three polycyclic aromatic compounds by human liver microsomes

Abstract

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 careinogens 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.