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在转染了人类代谢酶的细胞中对取代呋喃(2,5 - 二甲基呋喃和糠醇)的遗传毒性作用的体外研究。

An in vitro study on the genotoxic effect of substituted furans in cells transfected with human metabolizing enzymes: 2,5-dimethylfuran and furfuryl alcohol.

作者信息

Huffman Minor P, Høie Anja H, Svendsen Camilla, Brunborg Gunnar, Murkovic Michael, Glatt Hansruedi, Husøy Trine

机构信息

Department of Food, Water and Cosmetics, Norwegian Institute of Public Health (NIPH), NO-0403 Oslo, Norway.

Department of Chemicals and Radiation, National Institute of Public Health (NIPH), NO-0403 Oslo, Norway.

出版信息

Mutagenesis. 2016 Sep;31(5):597-602. doi: 10.1093/mutage/gew025. Epub 2016 May 25.

Abstract

2,5-Dimethylfuran (DMF) and furfuryl alcohol (FFA) are two substituted furans that are formed during the processing of foods and have also been used as food flavorings. DMF and FFA are proposed to be bioactivated by human sulfotransferases (SULTs) which are not expressed in conventional cell lines used for genotoxicity testing. Therefore, in addition to the standard V79 cell line, we used a transfected V79 derived cell line co-expressing human cytochrome P450 (CYP) 2E1 and human SULT1A1 to assess the genotoxicity of DMF and FFA. The alkaline single cell gel electrophoresis (SCGE) assay was used to detect DNA damage in the form of single strand breaks and alkali-labile sites after exposure to DMF (0.5h; 0.5, 1, 1.5 or 2mM) or FFA (3h; 1, 3, 6 or 15mM). DMF induced DNA damage in V79 cells in a concentration-dependent manner irrespective of the expression of human CYP2E1 and SULT1A1. Almost no increase in the level of DNA damage was detected after exposure to FFA, except for a weak effect at the highest concentration in the transfected cell line. The results suggest that DNA damage in V79 cells from exposure to DMF detected by the alkaline SCGE assay is independent of human CYP2E1 and SULT1A1, and the genotoxic effect of FFA, as assessed by SCGE, is minimal in V79 cells.

摘要

2,5-二甲基呋喃(DMF)和糠醇(FFA)是两种在食品加工过程中形成的取代呋喃,也被用作食品调味剂。据推测,DMF和FFA可被人类磺基转移酶(SULTs)生物活化,而这些酶在用于遗传毒性测试的传统细胞系中并不表达。因此,除了标准的V79细胞系外,我们还使用了一种共表达人类细胞色素P450(CYP)2E1和人类SULT1A1的转染V79衍生细胞系来评估DMF和FFA的遗传毒性。碱性单细胞凝胶电泳(SCGE)试验用于检测暴露于DMF(0.5小时;0.5、1、1.5或2毫摩尔)或FFA(3小时;1、3、6或15毫摩尔)后以单链断裂和碱不稳定位点形式存在的DNA损伤。无论人类CYP2E1和SULT1A1的表达如何,DMF均以浓度依赖性方式诱导V79细胞中的DNA损伤。暴露于FFA后,几乎未检测到DNA损伤水平的增加,除了在转染细胞系中最高浓度时有微弱影响。结果表明,通过碱性SCGE试验检测到的V79细胞因暴露于DMF而导致的DNA损伤与人类CYP2E1和SULT1A1无关,并且通过SCGE评估,FFA在V79细胞中的遗传毒性作用最小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28d1/4992344/5fd0d2a20c89/mutage_gew025_f0001.jpg

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