Dietary fat modulated metabolic fate of fluoranthene

膳食脂肪调节荧蒽的代谢命运

基本信息

批准号：
6595058
负责人：
Aramandla Ramesh
金额：
$ 14.55万
依托单位：
MEHARRY MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-05-06 至 2006-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6595058
关键词：
DNA damage adduct chemical carcinogen dietary lipid gastrointestinal toxin absorption heterocyclic polycyclic compound high performance liquid chromatography laboratory rat nutrient bioavailability pharmacokinetics thin layer chromatography toxin metabolism

项目摘要

DESCRIPTION (provided by applicant): Many hydrophobic and lipophilic environmental toxicants when consumed through diet are absorbed by passive diffusion across the gastrointestinal tract. The extent of absorption of these chemicals during gut passage and the factors governing their absorption are critical in determining the absorption efficiency of chemicals ingested through diet. In this research we will test the hypothesis that lipid load in the diet modulates fluoranthene (FLA; a toxic, and mutagenic polycyclic aromatic hydrocarbon compound) absorption resulting in conversion of FLA to its reactive metabolites in the body and in the extent of DNA-adduct formation. We propose the following three specific aims to test the hypothesis i) to study the bioavailability, metabolism and toxicokinetics of orally administered FLA and the fate of reactive metabolites in different concentrations of dietary fat and at different doses, ii) to estimate the disposition of FLA using a physiologically based pharmacokinetic model, and iii) to investigate the influence of dietary fat on formation and persistence of FLA-DNA adducts in target tissues. Our expectation is that findings from this research will provide us with a comprehensive picture of the fate and consequences of carcinogenic chemicals ingested through lipid rich diet. Results from these studies are significant in that they contribute to a greater understanding of the role played by dietary modulation on disposition of FLA in the body and the mechanisms by which bioavailable dose contributes to carcinogenicity.

描述（由申请人提供）：通过饮食消耗时，许多疏水和亲脂性环境有毒物质被被动扩散在胃肠道中吸收。这些化学物质在肠道通道过程中的吸收程度以及控制它们吸收的因素对于确定通过饮食摄入的化学物质的吸收效率至关重要。在这项研究中，我们将测试饮食中的脂质负荷可调节氟烷烷（FLA；一种有毒和诱变的多环芳烃烃化合物）的吸收，从而导致FLA转化为其在体内的反应性代谢产物，并在DNA-辅助形成的程度上转化为反应性代谢物。我们提出以下三个特定旨在检验假设i）以研究口服fla的生物利用性，代谢和毒性动力学，以及不同浓度的饮食脂肪和不同剂量的反应性代谢物的命运，ii），ii），以对基于物理学的脂肪进行饮食的限制，以估算FLA的饮食习惯，并研究饮食习惯，并在III和III上进行了饮食的影响）目标组织中的FLA-DNA加合物。我们的期望是，这项研究的发现将为我们提供有关通过富含脂质的饮食摄入的致癌化学物质的命运和后果的全面了解。这些研究的结果很重要，因为它们有助于更深入地了解饮食调制对FLA在体内处置的作用以及可生物可利用剂量有助于致癌性的机制。