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 benzo[f]quinoline which were identified were 7,8-dihydroxy-7,8-dihydrobenzo[f]quinoline, 9,10-dihydroxy-9,10-dihydrobenzo[f]quinoline, 7-hydroxybenzo[f]quinoline, and benzo[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 formation of both of these dihydrodiols can be inhibited. The major metabolites of benzo[h]quinoline were identified as 5,6-dihydroxy-5,6-dihydrobenzo[h]quinoline and 7,8-dihydroxy-7,8-dihydrobenzo[h]quinoline. Benzo[h]quinoline-N-oxide was not detected as a metabolite. In the presence of an epoxide hydratase inhibitor, the major metabolites of benzo[h]quinoline were 5,6-epoxybenzo[h]quinoline and 7-hydroxybenzo[h]quinoline. The difference in the metabolism to N-oxides observed between benzo[h]quinoline and benzo[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.