The effect of knockout of sulfotransferases 1a1 and 1d1 and of transgenic human sulfotransferases 1A1/1A2 on the formation of DNA adducts from furfuryl alcohol in mouse models.
The effect of knockout of sulfotransferases 1a1 and 1d1 and of transgenic human sulfotransferases 1A1/1A2 on the formation of DNA adducts from furfuryl alcohol in mouse models.
复制标题
敲除磺基转移酶 1a1 和 1d1 以及转基因人磺基转移酶 1A1/1A2 对小鼠模型中糠醇 DNA 加合物形成的影响
DOI：
10.1093/carcin/bgu152
复制
发表时间：
2014
期刊：
影响因子：
4.7
通讯作者：
Monien
中科院分区：
文献类型：
--
作者：
Sachse;Monien
糠醇是一种存在于许多食品中的啮齿动物致癌物。磺基转移酶（SULT）将糠醇转化为DNA反应性和致突变性2-磺酰甲基呋喃。建立了同位素稀释超高效液相色谱-串联质谱联用技术定量测定DNA加合物N2-（（呋喃-2-基）甲基）-2′-脱氧鸟苷（N2-MF-dG）的方法。为了更好地了解特定SULT形式对体内糠醇遗传毒性的贡献，我们研究了N2-MF-dG在不同小鼠模型中的组织分布。对表达不同人和鼠SULT形式的鼠伤寒沙门氏菌菌株进行的早期致突变性研究表明，人SULT 1A 1和鼠SULT 1a 1和1d 1最有效地催化糠醇磺基结合。在这里，我们使用了三个小鼠系来研究小鼠SULT，FVB/N野生型（wt）小鼠和两个缺乏小鼠Sult 1a 1或Sult 1d 1的转基因模型对糠醇的生物活化作用。动物接受单剂量的糠醇，并在肝、肾、肺、结肠和小肠中测定DNA加合物的水平。Sult 1d 1基因缺失对糠醇遗传毒性的影响是中等的，仅限于肾脏和小肠。相反，功能性Sult 1a 1的缺失对加合物水平产生了巨大的影响，与野生型动物相比，雌性Sult 1a 1缺失小鼠的所有组织中的加合物水平降低了33-73%。在表达hSULT 1A 1/1A 2而不是内源性Sult 1a 1和Sult 1d 1的人源化小鼠系中检测到高N2-MF-dG水平支持了以下假设：在人类中，糠醇也转化为致突变的2-磺酰甲基呋喃。
Furfuryl alcohol is a rodent carcinogen present in numerous foodstuffs. Sulfotransferases (SULTs) convert furfuryl alcohol into the DNA reactive and mutagenic 2-sulfoxymethylfuran. Sensitive techniques for the isotope-dilution ultra performance liquid chromatography–tandem mass spectrometry quantification of resulting DNA adducts, e.g.N2-((furan-2-yl)methyl)-2′-deoxyguanosine (N2-MF-dG), were developed. To better understand the contribution of specific SULT forms to the genotoxicity of furfuryl alcoholin vivo, we studied the tissue distribution ofN2-MF-dG in different mouse models. Earlier mutagenicity studies withSalmonella typhimuriumstrains expressing different human and murine SULT forms indicated that human SULT1A1 and murine Sult1a1 and 1d1 catalyze furfuryl alcohol sulfo conjugation most effectively. Here, we used three mouse lines to study the bioactivation of furfuryl alcohol by murine SULTs, FVB/N wild-type (wt) mice and two genetically modified models lacking either murine Sult1a1 or Sult1d1. The animals received a single dose of furfuryl alcohol, and the levels of the DNA adducts were determined in liver, kidney, lung, colon and small intestine. The effect ofSult1d1gene disruption on the genotoxicity of furfuryl alcohol was moderate and limited to kidney and small intestine. In contrast, the absence of functional Sult1a1 had a massive influence on the adduct levels, which were lowered by 33–73% in all tissues of the femaleSult1a1null mice compared with the wt animals. The detection of highN2-MF-dG levels in a humanized mouse line expressing hSULT1A1/1A2 instead of endogeneous Sult1a1 and Sult1d1 supports the hypothesis that furfuryl alcohol is converted to the mutagenic 2-sulfoxymethylfuran also in humans.
登录
查看更多内容
影响因子：
4.1
作者：
Teubner, Wera;Meinl, Walter;Glatt, Hansruedi
通讯作者：
Glatt, Hansruedi
处理呋喃树脂砂的造型工和制芯工的肺功能受损
DOI：
10.1007/bf00381565
发表时间：
1991
影响因子：
3
作者：
Mats Åkhman;R. Alexandersson;U. Ekholm;B. Bergstrom;Monica Dahlgvist;U. Ulfvarson
通讯作者：
U. Ulfvarson
影响因子：
4.7
作者：
Monien, Bernhard H.;Herrmann, Kristin;Glatt, Hansruedi
通讯作者：
Glatt, Hansruedi
影响因子：
3.8
作者：
Alnouti, Yazen;Klaassen, Curtis D.
通讯作者：
Klaassen, Curtis D.
影响因子：
3.5
作者：
Hebbring, Scott J.;Adjei, Araba A.;Thibodeau, Stephen N.
通讯作者：
Thibodeau, Stephen N.