Identification of the metabolites of benzo[f]quinoline and benzo[h]-quinoline formed by rat liver homogenate

Benzo[f]quinoline and benzo[h]quinoline are widespread environmentalpollutants which have been found to be mutagenic. The metabolismof benzo[f]quinoline and benzo[h]quinoline was investigatedusing a liver homogenate from Aroclor-pretreated rats. The metabolitesof benzof[f]-quinoline which were identified were 7,8-dihydroxy-7,8-di-hydrobenzo[f]quinoline,9,10-dihydroxy-9,10-dihydrobenzo-[f]quinoline, 7-hydroxybenzo[f]quinoline,and benzof[f]-quinoline-N-oxide. Metabolism studies on benzo[f]quinolineperformed in the presence of the epoxide hydratase inhibitor,3,3,3-trichloropropylene oxide, demonstrated that the formation of both of these dihydrodiols can be inhibited. The major metabolites of benzo[h]quinoline were identified as 5,6-di-hydroxy-5,6-dihydrobenzo[h]quinolineand 7,8-dihydroxy-7,8-dihydrobenzo[h]quinoline. Benzo[h]quinoIine-N-oxidewas not detected as a metabolite. In the presence of an epoxide hydratase inhibitor, the major metabolites of benzof[h]-quinolinewere 5,6-epoxybenzo[h]quinoline and 7-hydroxy-benzo[h]quinoline.The difference in the metabolism to N-oxides observed betweenbenzo[h]quinoline and benzof[f]-quinoline is consistent withprevious observations in which sterically hindered aromaticring nitrogen compounds such as benzo[h]quinoline are more resistantto N-oxide formation. The nitrogen atom of these aza-areneswith its lone pair of electrons has a significant influenceon sites at which dihydrodiols are formed. The data suggestthat the aromatic ring nitrogen of these azaphenanthrenes hasan effect similar to that of a methyl substituent in directingtheir metabolic oxidation.