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Fungal metabolism and detoxification of fluoranthene
J V Pothuluri1, R H Heflich, P P Fu
1National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079.
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.
Insights
Cunninghamella elegans detoxifies fluoranthene (FA), reducing its mutagenic potential. Fungal metabolites, unlike those from rat liver, showed reduced or no mutagenicity, indicating detoxification pathways.
Area of Science:
- Environmental Science
- Biotechnology
- Toxicology
Background:
- Fluoranthene (FA) is a polycyclic aromatic hydrocarbon with known mutagenic properties.
- Biotransformation by microorganisms like Cunninghamella elegans can alter the toxicity of environmental pollutants.
- Understanding microbial detoxification pathways is crucial for environmental risk assessment.
Purpose of the Study:
- To investigate the mutagenic activity of FA metabolites produced by Cunninghamella elegans.
- To compare the mutagenicity of fungal FA metabolites with those produced by rat liver systems.
- To assess the role of stereochemistry in the mutagenic potential of FA metabolites.
Main Methods:
- Metabolites of FA produced by Cunninghamella elegans were identified.
- Mutagenicity assays were performed using Salmonella typhimurium strains TA100 and TA104.
- Comparative studies utilized rat liver microsomes and high-performance liquid chromatography.
- Circular dichroism spectroscopy was employed to determine optical activity.
Main Results:
- FA exhibited dose-related mutagenicity in the presence of rat liver homogenate.
- Most FA metabolites from Cunninghamella elegans, including FA trans-2,3-dihydrodiol, showed no mutagenic activity.
- 9-Hydroxy-FA trans-2,3-dihydrodiol displayed weak mutagenicity.
- Fungal FA trans-2,3-dihydrodiol lacked optical activity, unlike the optically active rat liver metabolite.
- Mutagenic activity decreased over a 120-hour incubation period.
Conclusions:
- Cunninghamella elegans possesses the capability to detoxify fluoranthene.
- The stereochemistry of the fungal FA trans-2,3-dihydrodiol metabolite contributes to its reduced mutagenic potential compared to the rat liver metabolite.
- Microbial biotransformation offers a potential strategy for mitigating the risks associated with FA exposure.