Effect of dietary fat on metabolism and DNA adduct formation after acute oral exposure of F-344 rats to fluoranthene.
Effect of dietary fat on metabolism and DNA adduct formation after acute oral exposure of F-344 rats to fluoranthene.
复制标题
膳食脂肪对 F-344 大鼠急性口服荧蒽后代谢和 DNA 加合物形成的影响。
DOI：
10.1016/j.jnutbio.2006.04.001
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Ramesh,Aramandla
中科院分区：
文献类型：
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作者：
Walker,StormyA;Addai,AmmaB;Mathis,Malcolm;Ramesh,Aramandla
对健康的不利影响，如癌症和毒性，可能归因于食用受化学污染的富含脂肪的食物。这会导致体内更多的亲脂性有毒化学物质的摄入和滞留，从而增加对人类健康的风险。本研究的目的是研究膳食脂肪对多环芳烃化合物荧蒽(Fla)的处置和代谢的影响。以单不饱和脂肪(花生油)、多不饱和脂肪(玉米油)和饱和脂肪(椰子油)灌胃给F344大鼠，剂量分别为50和100μg/kg。于暴露后不同时间点采集血液、小肠、肝脏、肺、睾丸、脂肪组织、尿便。样品用反相高效液相色谱法分析FLA母体化合物和代谢物。从组织中提取DNA，进行32P-后标记以测定FLA-DNA加合物。与单一不饱和脂肪组和多不饱和脂肪组相比，饱和脂肪治疗组未改变的FLA(FLA母体化合物)及其代谢产物浓度升高。通过饱和脂肪摄入FLA的大鼠组织中FLA-DNA加合物浓度较高。药物动力学参数、Fla代谢物和Fla-DNA加合物浓度呈剂量依赖性增加，其中饱和脂肪的增加具有统计学意义(P<；0.05)。这些发现清楚地表明，FLA母体化合物在饱和脂肪中的长时间停留允许广泛的新陈代谢，导致FLA的反应性代谢产物与DNA结合，并在长期暴露的情况下造成显著损害。
Adverse health effects such as cancer and toxicity may be attributed to consumption of chemically contaminated food rich in fat. This leads to a larger intake and retention of lipophilic toxic chemicals in the body with an increase in risks to human health. The objective of this study was to characterize the effect of dietary fat on disposition and metabolism of fluoranthene (FLA), a polycyclic aromatic hydrocarbon compound. FLA was administered to F-344 rats in monounsaturated (peanut oil), polyunsaturated (corn oil) and saturated (coconut oil) fats at doses of 50 and 100 μg/kg via oral gavage. Blood, small intestine, liver, lung, testis, adipose tissue, urine and feces were collected at various time points' post-FLA exposure. Samples were analyzed by reverse-phase high-performance liquid chromatography for FLA parent compound and metabolites. DNA was isolated from the tissues and subjected to32P-post labeling to measure FLA–DNA adducts. The concentrations of unchanged FLA (FLA parent compound) and its metabolites showed an increase for the saturated fat treatment group compared with mono- and polyunsaturated fat groups. The FLA–DNA adduct concentrations were high in tissues of rats that received FLA through saturated fat. The toxicokinetic parameters, concentrations of FLA metabolites and FLA–DNA adduct showed a dose-dependent increase, and this increase was statistically significant (P<.05) for saturated fat. These findings clearly demonstrate that the high residence time of FLA parent compound in saturated fat allows extensive metabolism, contributing reactive metabolites of FLA that bind with DNA and causing marked damage in a long-term exposure scenario.