Ethanol and 4-methylpyrazole increase DNA adduct formation of furfuryl alcohol in FVB/N wild-type mice and in mice expressing human sulfotransferases 1A1/1A2.
Ethanol and 4-methylpyrazole increase DNA adduct formation of furfuryl alcohol in FVB/N wild-type mice and in mice expressing human sulfotransferases 1A1/1A2.
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乙醇和 4-甲基吡唑增加 FVB/N 野生型小鼠和表达人磺基转移酶 1A1/1A2 的小鼠中糠醇 DNA 加合物的形成
DOI：
10.1093/carcin/bgw006
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发表时间：
2016
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（FFA）是一种致癌的食品污染物，它是由果糖和葡萄糖在酸和热催化下降解形成的。通过磺基转移酶（SULT）的活化产生DNA反应性和致突变性硫酸酯。在FFA处理的小鼠和人体组织样本中检测到最显著的DNA加合物N2-（（呋喃-2-基）甲基）-2′-脱氧鸟苷（N2-MF-dG）。游离脂肪酸解毒的主要途径是通过醇脱氢酶（ADHS）和醛脱氢酶（ALDH）进行氧化。这些酶的活性在抑制剂或竞争性底物的存在下可以大大改变。在这里，我们研究了乙醇和ADH抑制剂4-甲基吡唑（4 MP）对野生型和人源化小鼠（转基因人SULT 1A 1/1A 2和小鼠（m）Sult 1a 1和Sult 1d 1基因（h1 A1/1A 2/1a 1 −/1d 1 −）缺陷）中FFA形成DNA加合物的影响。FFA单独给药导致雄性和雌性野生型小鼠分别产生4.5N2-MF-dG/108核苷和33.6N2-MF-dG/108核苷的肝加合物水平，以及雄性和雌性h1 A1/1A 2/1a 1 −/1d 1 −小鼠分别产生19.6N2-MF-dG/108核苷和95.4N2-MF-dG/108核苷的肝加合物水平。同时给予1.6g乙醇/kg体重，雄性野生型小鼠的N2-MF-dG水平增加了2.3倍，雌性野生型小鼠增加了1.7倍，雄性h1 A1/1A 2/1a 1 −/1d 1 −小鼠增加了2.5倍，雌性增加了1.5倍。联合给予100 mg 4 MP/kg体重对加合物水平具有相似的影响。这些发现表明，氧化代谢的调节剂，例如药物4 MP或酒精饮料的消费，可能会增加FFA对人类的遗传毒性作用。
Furfuryl alcohol (FFA) is a carcinogenic food contaminant, which is formed by acid- and heat-catalyzed degradation of fructose and glucose. The activation by sulfotransferases (SULTs) yields a DNA reactive and mutagenic sulfate ester. The most prominent DNA adduct,N2-((furan-2-yl)methyl)-2′-deoxyguanosine (N2-MF-dG), was detected in FFA-treated mice and also in human tissue samples. The dominant pathway of FFA detoxification is the oxidation via alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs). The activity of these enzymes may be greatly altered in the presence of inhibitors or competitive substrates. Here, we investigated the impact of ethanol and the ADH inhibitor 4-methylpyrazole (4MP) on the DNA adduct formation by FFA in wild-type and in humanized mice that were transgenic for humanSULT1A1/1A2and deficient in the mouse (m)Sult1a1andSult1d1genes (h1A1/1A2/1a1−/1d1−). The administration of FFA alone led to hepatic adduct levels of 4.5N2-MF-dG/108nucleosides and 33.6N2-MF-dG/108nucleosides in male and female wild-type mice, respectively, and of 19.6N2-MF-dG/108nucleosides and 95.4N2-MF-dG/108nucleosides in male and female h1A1/1A2/1a1−/1d1−mice. The coadministration of 1.6g ethanol/kg body weight increasedN2-MF-dG levels by 2.3-fold in male and by 1.7-fold in female wild-type mice and by 2.5-fold in male and by 1.5-fold in female h1A1/1A2/1a1−/1d1−mice. The coadministration of 100mg 4MP/kg body weight had a similar effect on the adduct levels. These findings indicate that modulators of the oxidative metabolism, e.g. the drug 4MP or consumption of alcoholic beverages, may increase the genotoxic effects of FFA also in humans.
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酒精与癌症。
影响因子：
--
作者：
Rogers,AE;Conner,MW
通讯作者：
Conner,MW
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
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
影响因子：
4.7
作者：
Sachse;Monien
通讯作者：
Monien
影响因子：
7.4
作者：
Monien, Bernhard H.;Schumacher, Fabian;Herrmann, Kristin;Glatt, Hansruedi;Turesky, Robert J.;Chesne, Christophe
通讯作者：
Chesne, Christophe