Identification of Mutagenic Metabolites Formed by C-Hydroxylation and Nitroreduction of 5-Nitroacenaphthene in Rat Liver¹

The metabolism of the mutagen and carcinogen, 5-nitroacenaphthene, by the 9000 × g supernatant from the livers of Aroclor-pretreated rats was studied. The major primary metabolites were 1-hydroxy-5-nitroacenaphthene and 2-hydroxy-5-nitroacenaphthene. These metabolites were oxidized to 1-oxo-5-nitroacenaphthene and 2-oxo-5-nitroacenaphthene, hydroxylated to cis-1,2-dihydroxy-5-nitroacenaphthene and trans-1,2-dihydroxy-5-nitroacenaphthene, and reduced to 1-hydroxy-5-aminoacenaphthene and 2-hydroxy-5-aminoacenaphthene and 2-hydroxy-5-aminoacenaphthene. Reduction of 1-and 2-oxo-5-nitroacenaphthene to 1-oxo- and 2-oxo-5-aminoacenaphthene was also observed. When incubations were carried out in a N₂-enriched atmosphere (10% O₂ in N₂), the major metabolites were 1-hydroxy-and 2-hydroxy-5-nitroacenaphthene and 2-oxo-5-aminoacenaphthene. Selected metabolites were tested for mutagenicity toward Salmonella typhimurium TA 98. The most mutagenic of the metabolites tested, in the presence or absence of rat liver 9000 × g supernatant, were 1-hydroxy-5-nitroacenaphthene and 1-oxo-5-nitroacenaphthene. These results indicate that the 9000 × g supernatant from the livers of Aroclor-pretreated rats is capable of catalyzing both the oxidation and reduction of 5-nitroacenaphthene and that the reduced derivatives of 1-hydroxy- or 2-hydroxy- or 1-oxo- or 2-oxo-5-nitroacenaphthene are proximate mutagens.