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

Abstract

The present study was conducted to investigate whether colon tumors were capable of metabolizing benzo (a)pyrene (BaP), and fluoranthene (FLA), two toxicants that belong to the polycyclic aromatic hydrocarbon family of compounds. Microsomes were isolated from the colon tumors of ApcMin mice that received subchronic doses of 50 μg/kg BaP and incubated with either BaP or FLA (3 μM each) alone or in combination and appropriate control groups that received nothing. Subsequent to incubation, samples were extracted with ethyl acetate and analyzed for BaP and FLA metabolites by reverse-phase HPLC equipped with fluorescence detection. Microsomes from tumor tissues were found to metabolize BaP to a greater extent than those from the non-tumor tissues. The rate of BaP metabolism (picomoles of metabolite per minute per milligram of protein) was found to be more when microsomes from BaP-pretreated mice were exposed to BaP alone and FLA in combination with BaP, compared to controls. The microsomes from BaP-preexposed mice generated greater proportion of BaP 7,8-diol and BaP 3,6- and 6,12-diones compared to other experimental groups. Additionally, microsomes from BaP-pretreated mice produced greater proportion of FLA 2, 3-diol and 2, 3 D FLA when microsomes were incubated with FLA alone or a combination of BaP and FLA. Our studies revealed that the tumor microsomes were competent to metabolize BaP and FLA either singly or in combination. The biotransformation of BaP and FLA as a consequence of prior and simultaneous exposure to BaP may influence the growth of tumors. Our findings may have relevance to human long-term dietary intake of these toxicants and the consequent acceleration of the colon carcinogenesis process.

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

“…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.…”

“…Disposition of some PAH metabolites in intestinal crypts (Herbst et al, 2006) and the ability of tumor cells to metabolize BaP (Diggs et al, 2012) lend credence to the assumption that localized metabolism of PAHs contribute to cytotoxicity and aid in the neoplastic transformation of polyps.…”

A review of airborne polycyclic aromatic hydrocarbons (PAHs) and their human health effects

“…Long-term exposure to low levels of some PAHs (e.g., pyrene and BaP) has been identified as the cause of cancer in laboratory animals (Diggs et al, 2012). Animal studies have also shown adverse reproductive and developmental effects from PAH exposure while such effects have not commonly been detected in humans (Wells et al, 2010).…”

Metabolism of benzo(a)pyrene by aortic subcellular fractions in the setting of abdominal aortic aneurysms

“…The greater concentrations of B(a)P metabolites may have elevated plasma ROS levels and increased protein expression of TNF-a, Cyp A, and MMP-9 leading to the pathobiology of abdominal aneurysms observed in our earlier study. Among the different subcellular fractions, the microsomal and mitochondrial fractions registered greater concentrations of B(a)P metabolites as these organelles are rich in CYP family of biotransformation enzymes [39].…”