Mutagenic properties of a nitrofuran, 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000), in lacI transgenic mice
Mutagenic properties of a nitrofuran, 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000), in lacI transgenic mice
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DOI：
10.1016/s1383-5718(00)00103-0
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发表时间：
2000-10-31
影响因子：
1.9
通讯作者：
Touati, E
中科院分区：
文献类型：
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作者：
Quillardet, P;Michel, V;Touati, E
已经在细菌中广为人知的5-硝基呋喃7-甲氧基-2-硝基呋喃[2,1-b]呋喃（R7000）的体内诱变特性在lad转基因小鼠中进行了评估（Big Blue）。测定了ipp处理小鼠各器官的突变频率，并测定了突变诱导显著的靶器官的诱导突变性质。研究发现，R7000对小鼠具有诱变作用，但与其他已知的诱变化学物质相比，基于每单位质量诱导突变体的数量，R7000对小鼠的诱变作用似乎远低于对细菌的诱变作用。受影响最严重的器官是小肠、盲肠和结肠器官，它们属于消化器官。从转基因小鼠小肠中恢复的lad基因中r7000诱导的突变分布与大肠杆菌中发现的突变分布非常相似。小鼠与大肠杆菌在R7000诱导突变谱上的差异主要体现在单碱基移帧与碱基替换的比例上。由于R7000诱导的突变似乎出现在干细胞群体中，并且干细胞对致癌作用很重要，因此我们的结果与R7000和其他硝基呋喃可能的致癌作用相一致。(C) 2000 Elsevier Science B.V.版权所有
The in vivo mutagenic properties of a 5-nitrofuran, the 7-methoxy-2-nitranaphtho[2,1-b]furan (R7000), already well known in bacteria, was evaluated in lad transgenic mice (Big Blue). The mutation frequency was determined in various organs of i.p. - treated mice and the nature of induced mutations was determined for the target organs in which mutation induction was significant. It was found that R7000 is mutagenic in mice, although, on the basis of the number of induced mutants per unit mass in comparison with other known mutagenic chemicals, R7000 appears to be considerably less mutagenic in mice than in bacteria. The most affected organs, small intestine, caecum and colon organs belong to the digestive apparatus. The distribution of R7000-induced mutations in the lad gene recovered from small intestine of transgenic mice was very similar to that which had been found in E. coli. The difference between mouse and E, coli in the R7000 induced mutational spectra are mainly in the proportion of single base frameshifts versus base substitutions. Since R7000 induced mutations seemed to arise in the population of stem cells and that the stem cells are important for carcinogenesis, our results are compatible with a possible carcinogenic effect of R7000 and other nitrofurans. (C) 2000 Elsevier Science B.V. All rights reserved.