Fungal metabolism of nitrofluoranthenes

Metabolism of 2-nitrofluoranthene (2-NFA), one of the most abundant and genotoxic environmental pollutants in air, and of a mixture of 2-nitrofluoranthene and 3-nitrofluoranthene (3-NFA) was studied using (1) the fungus Cunninghamella elegans ATCC 36112 and (2) rat liver microsomes. The fungal metabolites were separated by reversed-phase high-performance liquid chromatography (HPLC) and identified by 1H nuclear magnetic resonance (NMR) spectrometry, ultraviolet (UV)-visible spectroscopy, and online atmospheric-pressure chemical ionization/mass spectrometry (APCI/MS). The fungus metabolized 82% of 2-nitro-[3H]-fluoranthene to 2-nitrofluoranthene 8-sulfate and 2-nitrofluoranthene 9-sulfate. Metabolism of a mixture of 2- and 3-nitrofluoranthene by C. elegans similarly produced 2-nitrofluoranthene 8- and 9-sulfate and 3-nitrofluoranthene 8- and 9-sulfate as major metabolites. In addition, a glucoside conjugate of 3-hydroxy-2-nitrofluoranthene was tentatively identified by APCI/MS analysis. When rat liver microsomes were incubated with a mixture of 2- and 3-nitrofluoranthene for 1 h, in addition to the trans-7,8- and 9,10-dihydrodiols reported previously for 2-nitrofluoranthene, several novel metabolites were produced including 2-nitrofluoranthene trans-4,5-dihydrodiol and 2-nitrofluoranthene trans-8,9-dihydrodiol, the trans-4,5-dihydrodiol of 3-nitrofluoranthene, and phenolic products of both 2- and 3-nitrofluoranthene. The fungal metabolism of the 2- and 3-nitrofluoranthene mixture was similar to the metabolism of individual nitrofluoranthenes; however, the mammalian metabolism of the nitrofluoranthene mixture showed differences in regioselectivity at positions C4, C5, C8, and C9.