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

Division of Chemical Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595

The metabolism of the mutagen and carcinogen, 5-nitroacenaphthene, by the 9000 x 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 x g supernatant, were 1-hydroxy-5-nitroacenaphthene and 1-oxo-5-nitroacenaphthene. These results indicate that the 9000 x 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.

¹ A portion of this study was presented at the 72nd Annual Meeting of the American Association for Cancer Research, Washington, D. C., April 1981 (4). This is Paper 40 in "A Study of Chemical Carcinogenesis." This publication is dedicated to the founder of the American Health Foundation, Dr. Ernst L. Wynder, on the occasion of the 10th anniversary of the Naylor Dana Institute for Disease Prevention.

² Recipient of the National Institute of Environmental Health Sciences Award ES02477-01. To whom requests for reprints should be addressed.

Received 8/31/81. Accepted 1/ 4/82.

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