Time course of oxidative benz[a]anthracene metabolism by liver microsomes of normal and PCB-treated rats.

The time course for the oxidative metabolism of benz[a]anthracene by liver microsomes of normal, 3,3',4,4'-tetrachlorobiphenyl-(TCBP) and polychlorinated biphenyl-(PCB) treated rats has been investigated. These are shown not to be linear in all cases. In normal microsomes the 10,11-dihydrodiol is the main metabolite, followed by the 5,6- and 8,9-dihydrodiols. Secondary metabolism, i.e. formation of dihydrodiol epoxides, is observed only after 5 min. In contrast, TCBP microsomes produced predominantly the 5,6-dihydrodiol followed by the 8,9-dihydrodiol, whereas the formation of the 10,11-dihydrodiol is suppressed. Metabolism deriving from oxidation of the 5,6-position is increased 15-20 fold; again secondary metabolites occur between the 5th and 10th min of incubation. Gas chromatography and mass spectra data suggests the formation of the ultimate carcinogen, 3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenz[a]anthracene, as concluded from detection of its rearrangement product, the 2,3,4-triol. In PCB-treated rats secondary metabolism is observed within 2.5 min. 5,6-Oxidation is increased 27 fold, 8,9-oxidation 10 fold, but 10,11-oxidation is completely suppressed. The above-mentioned ultimate carcinogen is also formed. Moreover, a series of tetrols is detected. Optimum incubation times dependent on the problem under study are discussed.