Effect of benzo(a)pyrene exposure on fluoranthene metabolism by mouse adipose tissue microsomes

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 μg/kg BaP and incubated with FLA (3μM) 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-pretreated mice produced 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-pretreated mice were co-incubated with BaP and FLA, than 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.

Tumor microsomal metabolism of the food toxicant, benzo(a)pyrene, in Apc Min mouse model of colon cancer

“…Our findings are in agreement with that of Vaca et al [30] and Huderson et al [31] who have shown that pretreatment with BaP induces the microsomal metabolism of BaP to precursors of reactive metabolites. Conceivably biotranformation of BaP by tumor cells may lead to localized production of intracellular metabolites [32, 33] and may therefore have a role to play not only in the causation but also in the progression of disease as well.…”

Benzo(a)pyrene modulates fluoranthene-induced cellular responses in HT-29 colon cells in a dual exposure system

“…Induction of CYP enzymes by BaP may have modulated the enzymatic metabolic activation of FLA thereby enhancing its carcinogenic potential. Our findings are in agreement with that of Vaca et al (1992) and Huderson et al (2010) who have shown that co-treatment with BaP induces the microsomal metabolism of FLA to precursors of reactive metabolites. Bio-tranformation of FLA by tumor cells may lead to production of intracellular metabolites (Buesen et al, 2002; Myers et al, 2011) whose production rate may have enhanced due to the action of BaP.…”

“…The FLA metabolite types identified in our study are in agreement with published literature, which used microsomes from intestinal, hepatic and extra-hepatic tissues (Walker et al, 2006; Huderson et al, 2010; Diggs et al, 2012). While colon cells could metabolize FLA, the generation of FLA 2,3-diol in greater proportions when cells were treated with FLA together with BaP is noteworthy due to the ability of this metabolite to bind to cellular macromolecules such as DNA and proteins (Babson et al, 1986; Hutchins et al, 1988).…”

“…These findings lend credence to our supposition that the presence of another PAH compound in a mixture will have a bearing on the metabolism of the chemical in question. Additionally, our earlier studies have shown an enhanced metabolism of FLA when microsomes from adipose tissue (Huderson et al, 2010) and colon tumors (Diggs et al, 2012) were exposed to BaP and FLA together.…”

“…Bio-tranformation of FLA by tumor cells may lead to production of intracellular metabolites (Buesen et al, 2002; Myers et al, 2011) whose production rate may have enhanced due to the action of BaP. Co-exposure to both BaP and FLA has been shown to enhance the metabolism of FLA in adipose (Huderson et al, 2010) and colon tumor (Diggs et al, 2012) tissues of a colon cancer mouse model. This situation may aid in the progression of disease as well.…”