FUNGAL METABOLISM OF NITROFLUORANTHENES

Metabolism of 2-nitrofluoranthene (2-NFA), one of the most abundant an d genotoxic environmental pollutants in air, and of a mixture of 2-nit rofluoranthene and 3-nitrofluoranthene (3-NFA) was studied using (1) t he fungus Cunninghamella elegans ATCC 36112 and (2) rat liver microsom es. The fungal metabolites were separated by reversed-phase high-perfo rmance liquid chromatography (HPLC) and identified by H-1 nuclear magn etic resonance (NMR) spectrometry, ultraviolet (UV)-visible spectrosco py, and online atmospheric-pressure chemical ionization/mass spectrome try (APCI/MS). The fungus metabolized 82% of 2-nitro-[H-3]-fluoranthen e to 2-nitrofluoranthene 8-sulfate and 2-nitrofluoranthene 9-sulfate. Metabolism of a mixture of 2- and 3-nitrofluoranthene by C. elegans si milarly produced 2-nitrofluoranthene 8- and 9-sulfate and 3-nitrofluor anthene 8- and 9-sulfate as major metabolites. In addition, a glucosid e conjugate of 3-hydroxy-2-nitrofluoranthene was tentatively identifie d 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 tra ns-7,8- and 9, 10-dihydrodiols reported previously for 2-nitrofluorant hene, several novel metabolites were produced including 2-nitrofluoran thene trans-4,5-dihydrodiol and 2-nitrofluoranthene trans-8,9-dihydrod iol, the trans-4,5-dihydrodiol of 3-nitrofluoranthene, and phenolic pr oducts of both 2- and 3-nitrofluoranthene. The fungal metabolism of th e 2- and 3-nitrofluoranthene mixture was similar to the metabolism of individual nitrofluoranthenes; however, the mammalian metabolism of th e nitrofluoranthene mixture showed differences in regioselectivity at positions C4, C5, C8, and C9.