Dose-dependent induction of rat liver microsomal aryl hydrocarbon monooxygenase by benzo[k]fluoranthene

The environmentally widespread polycyclic aromatic hydrocarbon (PAH) benzo[k]fluoranthene is a potent AHH inducer. This has been proven by recording the benz[a]anthracene metabolite profile in the rat liver by means of gas chromatography/mass spectrometry (GC/MS) technique. Even a total dose of 3 times 50 micrograms/kg body wt increases the metabolism of benz[a]anthracene by a factor of 2. The formation of the 8,9- as well as the 5,6-dihydrodiol is stimulated to about the same extent, whereas the formation of the 10,11-dihydrodiol is suppressed. After comparatively low doses of the inducer, a metabolite is formed which corresponds in all parameters with the postulated ultimate carcinogen 3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenz[a]anthracene. This metabolite and a number of other primary and secondary oxidation products could be identified after incubation with induced but not with normal microsomes. Therefore, it should be emphasised that metabolite profiles have to be recorded instead of measuring brutto conversions of PAH substrates to evaluate inducing effects.