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 environmental pollutants which have been found to be mutagenic. The metabolism of benzo[f]quinoline and benzo[h]quinoline was investigated using a liver homogenate from Aroclor-pretreated rats. The metabolites of 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]quinoline performed in the presence of the epoxide hydratase inhibitor, 3,3,3-trichloropropylene oxide, demonstrated that the forma tion of both of these dihydrodiols can be inhibited. The ma jor metabolites of benzo[h]quinoline were identified as 5,6-di-hydroxy-5,6-dihydrobenzo[h]quinoline and 7,8-dihydroxy-7,8-dihydrobenzo[h]quinoline. Benzo[h]quinoIine-N-oxide was not detected as a metabolite. In the presence of an epox ide hydratase inhibitor, the major metabolites of benzof[h]-quinoline were 5,6-epoxybenzo[h]quinoline and 7-hydroxy-benzo[h]quinoline. The difference in the metabolism to N-oxides observed between benzo[h]quinoline and benzof[f]-quinoline is consistent with previous observations in which sterically hindered aromatic ring nitrogen compounds such as benzo[h]quinoline are more resistant to N-oxide formation. The nitrogen atom of these aza-arenes with its lone pair of electrons has a significant influence on sites at which dihydrodiols are formed. The data suggest that the aromatic ring nitrogen of these azaphenanthrenes has an effect similar to that of a methyl substituent in directing their metabolic oxidation.