title: Fungal metabolism and detoxification of fluoranthene.
abstract: Five metabolites produced by Cunninghamella elegans from fluoranthene (FA) in biotransformation studies were investigated for mutagenic activity towards Salmonella typhimurium TA100 and TA104. Whereas FA displayed positive, dose-related mutagenic responses in both tester strains in the presence of a rat liver homogenate fraction, 3-FA-beta-glucopyranoside, 3-(8-hydroxy-FA)-beta-glucopyranoside, FA trans-2,3-dihydrodiol, and 8-hydroxy-FA trans-2,3-dihydrodiol were negative. 9-Hydroxy-FA trans-2,3-dihydrodiol showed a weak positive response in S. typhimurium TA100. Mutagenicity assays performed with samples extracted at 24-h intervals during incubation of C. elegans with FA for 120 h showed that mutagenic activity decreased with time. Comparative studies with rat liver microsomes indicated that FA trans-2,3-dihydrodiol, the previously identified proximal mutagenic metabolite of FA, was the major metabolite. The circular dichroism spectrum of the rat liver microsomal FA trans-2,3-dihydrodiol indicated that it was optically active. In contrast, the circular dichroism spectrum of the fungal FA trans-2,3-dihydrodiol showed no optical activity. These results indicate that C. elegans has the potential to detoxify FA and that the stereochemistry of its trans-2,3-dihydrodiol metabolite reduces its mutagenic potential.
authors.affiliation: National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079.
authors.forename: J V
authors.initials: JV
authors.lastname: Pothuluri
authors.forename: R H
authors.initials: RH
authors.lastname: Heflich
authors.forename: P P
authors.initials: PP
authors.lastname: Fu
authors.forename: C E
authors.initials: CE
authors.lastname: Cerniglia
mesh_terms: D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D005449:Fluorenes / Q000378:metabolism* / Q000633:toxicity; D009090:Mucorales / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
chemical_list: D005449:Fluorenes; D009153:Mutagens; C007738:fluoranthene