Metabolism of benzo(a)pyrene by aortic subcellular fractions in the setting of abdominal aortic aneurysms A. Ramesh 1 • P. A. Prins 2 • P. R. Perati 2 • P. V. Rekhadevi 1 • U. K. Sampson 2,3,4 Received: 16 September 2015 / Accepted: 29 October 2015 / Published online: 3 November 2015 Ó Springer Science+Business Media New York 2015 Abstract As exposure to polycyclic aromatic hydrocar- bons (PAHs; a family of environmental toxicants) have been implicated in cardiovascular diseases, the ability of the aortic tissue to process these toxicants is important from the standpoint of abdominal aortic aneurysms and atherosclerosis. Benzo(a)pyrene (B(a)P), a representative PAH compound is released into the environment from automobile exhausts, industrial emissions, and consider- able intake of B(a)P is also expected in people who are smokers and barbecued red meat eaters. Therefore, knowledge of B(a)P metabolism in the cardiovascular system will be of importance in the management of vas- cular disorders. Toward this end, subcellular fractions (nuclear, cytosolic, mitochondrial, and microsomal) were isolated from the aortic tissues of Apo E mice that received a 5 mg/kg/week of B(a)P for 42 days and 0.71 mg/kg/day for 60 days. The fractions were incubated with 1 and 3 lM B(a)P. Post incubation, samples were extracted with ethyl acetate and analyzed by reverse-phase HPLC. Microsomal B(a)P metabolism was greater than the rest of the fractions. The B(a)P metabolite levels generated by all the subcel- lular fractions showed a B(a)P exposure concentration- dependent increase for both the weekly and daily B(a)P treatment categories. The preponderance of B(a)P metabolites such as 7,8-dihydrodiol, 3,6-, and 6,12-dione metabolites are interesting due to their reported involve- ment in B(a)P-induced toxicity through oxidative stress. Keywords Benzo(a)pyrene Á Aortic aneurysms Á Atherosclerosis Á ApoE mouse Á Subcellular fractions Introduction Life style and environmental factors together play a major role in the etiology of human diseases. Dietary and smoking habits either individually or collectively introduce chemicals into the human body, which initiate disease by disrupting the metabolic homeostasis. Additionally, emis- sions from waste disposal, oil & gas exploration, and manufacturing processes release chemicals into the immediate environment near human habitation and trigger disease. One group of chemicals, which fits the above scenarios are polycyclic aromatic hydrocarbons (PAHs). Being combustion by-products and constituents of cigarette smoke, barbecued food, oil well fires, and automobile exhausts, these toxicants have been reported as causative agents of atherosclerosis [1], abdominal aneurysm [2], and peripheral arterial disease [3] both in animal models and humans. Inhalation exposure to benzo(a)pyrene (B(a)P) and other PAHs have been shown to have the highest rel- ative risk for fatal ischemic heart disease in people occu- pationally exposed to PAHs such as asphalt pavers and smokers [4]. Subsequent to exposure, PAHs cross through cell membranes and being lipophilic, undergo intracellular accumulation by concentrating in lipid droplets [5]. Studies from our research group have shown that PAHs through a & A. Ramesh aramesh@mmc.edu 1 Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, USA 2 Department of Medicine, Vanderbilt University Medical Center, Nashville, USA 3 Departments of Pathology, Immunology, and Microbiology, Vanderbilt University Medical Center, Nashville, USA 4 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, USA 123 Mol Cell Biochem (2016) 411:383–391 DOI 10.1007/s11010-015-2600-2