Effect of benzo(a)pyrene exposure on fluoranthene metabolism by mouse adipose tissue microsomes
Ashley C Huderson1, Deacqunita L Harris, Mohammad S Niaz
1Department of Biochemistry & Cancer Biology, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, TN 37208, USA.
Abstract:
The present study has been undertaken to examine whether exposure to benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound, influences the metabolism of fluoranthene (FLA), another PAH compound. Microsomes were isolated from the adipose tissue of mice that received 50 microg/kg BaP and incubated with FLA (3 microM) alone; FLA in combination with BaP at equimolar concentrations, and a control group that received nothing. Post-incubation, samples were extracted with ethyl acetate and analyzed for FLA metabolites by reverse-phase HPLC with fluorescence detection. The rate of FLA metabolism (pmol of metabolite/min/mg protein) was increased when microsomes from BaP-treated mice were exposed to FLA alone and FLA in combination with BaP, compared to controls. On the other hand, the difference in FLA metabolic rate between microsomes that were exposed to FLA + BaP was higher than the ones that received FLA. The microsomes from BaP-pre-treated mice produced a considerably higher proportion of FLA 2, 3-diol, and 2, 3 D FLA when microsomes were incubated with FLA. There were no differences in the FLA metabolite types formed when BaP-pre-treated mice were co-incubated with BaP and FLA than with FLA alone. The enhanced biotransformation of FLA as a result of prior and concomitant exposure to BaP may have implications for assessment of risks arising from human exposure to PAH mixtures.
Insights
Benzo(a)pyrene (BaP) exposure significantly increases fluoranthene (FLA) metabolism in mice. This enhanced biotransformation of FLA by BaP-exposed tissues impacts risk assessments for polycyclic aromatic hydrocarbon mixtures.
Area of Science:
- Environmental Chemistry
- Toxicology
- Biochemistry
Background:
- Polycyclic Aromatic Hydrocarbons (PAHs) are environmental contaminants.
- Benzo(a)pyrene (BaP) and fluoranthene (FLA) are common PAHs.
- Understanding PAH interactions is crucial for risk assessment.
Purpose of the Study:
- To investigate the effect of BaP exposure on FLA metabolism.
- To determine if BaP influences the rate and type of FLA metabolites produced.
Main Methods:
- Microsomes were isolated from adipose tissue of BaP-treated and control mice.
- Incubation of microsomes with FLA alone, or FLA with BaP.
- Analysis of FLA metabolites using High-Performance Liquid Chromatography (HPLC) with fluorescence detection.
Main Results:
- BaP exposure significantly increased the rate of FLA metabolism.
- Co-incubation with BaP showed a higher metabolic rate than FLA alone.
- FLA 2,3-diol and 2,3-D FLA were the predominant metabolites, with proportions altered by BaP exposure.
Conclusions:
- Prior and concurrent exposure to BaP enhances FLA biotransformation.
- This interaction has implications for human health risk assessments of PAH mixtures.
- Further research is needed to fully elucidate PAH metabolic interactions.
