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DOI10.1007/s13277-014-1647-0
Metabolism of benzo(a)pyrene by subcellular fractions of gastrointestinal (GI) tract and liver in Apc (Min) mouse model of colon cancer
Mantey, Jane A.1; Rekhadevi, Perumalla V.2; Diggs, Deacqunita L.2,3; Ramesh, Aramandla2
发表日期2014-05-01
ISSN1010-4283
卷号35期号:5页码:4929-4935
英文摘要

Given the fact that increased dietary intake of polycyclic aromatic hydrocarbons (PAHs; a family of environmental toxicants) leads to the formation and development of colon tumors, the ability of the gastrointestinal tract to process these compounds is important from the viewpoint of toxicity/carcinogenesis. Benzo(a)pyrene (BaP), a prototypical PAH compound is released into the environment from automobile exhausts, cigarette smoke, and industrial emissions. Additionally, considerable intake of BaP is expected in people who consume barbecued foods and a diet rich in saturated fat. In exposed animals, BaP becomes activated to potent metabolites that interfere with target organ function and as a consequence cause toxicity and cancer. Therefore, knowledge of BaP metabolism in the digestive system will be of importance in the management of cancers of the digestive tract. The objective of our study was to study the metabolism of BaP by subcellular fractions (nuclear, cytosolic, mitochondrial, and microsomal) of the gastrointestinal tract and liver. Subcellular fractions were isolated by differential centrifugation from the stomach, jejunum, colon, and liver tissues of Apc (Min) mice that received a subchronic dose of 25 mu g/kg BaP. The fractions were incubated with 1 and 3 mu M BaP. Subsequent to incubation, samples were extracted with ethyl acetate and analyzed for BaP metabolites by reverse-phase HPLC equipped with fluorescence detection. Among the different fractions tested, microsomal BaP metabolism was higher than the rest of the fractions in all the samples analyzed. Additionally, a BaP exposure concentration-dependent effect on metabolite levels generated by the subcellular fractions was recorded. The BaP metabolites identified were the following: BaP-9,10-diol; BaP-4,5-diol; BaP-7,8-diol; 9(OH) BaP; 3(OH) BaP; BaP-3,6-dione; and BaP-6,12-dione. While the diol group of metabolites was frequently detected, among diones, the 3,6 and 6,12-dione metabolites were infrequently detected. Among the diol metabolites, the preponderance of BaP-7,8-dihydrodiol is interesting, since this metabolite is a precursor to the DNA-reactive BaP-7,8-dihydrodiol epoxide (BPDE) that has been linked to BaP-induced cancer.


英文关键词Benzo(a) pyrene;Jejunum;Colon;Liver;Metabolism;Cancer
语种英语
WOS记录号WOS:000335759800115
来源期刊TUMOR BIOLOGY
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/57384
作者单位1.Meharry Med Coll, Dept Neurosci & Pharmacol, Nashville, TN 37208 USA;
2.Meharry Med Coll, Dept Biochem & Canc Biol, Nashville, TN 37208 USA;
3.US EPA, Toxic Assessment Div, Off Res & Dev, Res Triangle Pk, NC 27711 USA
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GB/T 7714
Mantey, Jane A.,Rekhadevi, Perumalla V.,Diggs, Deacqunita L.,et al. Metabolism of benzo(a)pyrene by subcellular fractions of gastrointestinal (GI) tract and liver in Apc (Min) mouse model of colon cancer[J]. 美国环保署,2014,35(5):4929-4935.
APA Mantey, Jane A.,Rekhadevi, Perumalla V.,Diggs, Deacqunita L.,&Ramesh, Aramandla.(2014).Metabolism of benzo(a)pyrene by subcellular fractions of gastrointestinal (GI) tract and liver in Apc (Min) mouse model of colon cancer.TUMOR BIOLOGY,35(5),4929-4935.
MLA Mantey, Jane A.,et al."Metabolism of benzo(a)pyrene by subcellular fractions of gastrointestinal (GI) tract and liver in Apc (Min) mouse model of colon cancer".TUMOR BIOLOGY 35.5(2014):4929-4935.
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