Quillardet P, Michel V, Arrault X, Hofnung M, Touati E
Unité de Programmation Moléculaire et Toxicologie Génétique, CNRS Ura 1444, Institut Pasteur, 25 rue du Dr Roux, 75724 Cedex 15, Paris, France.
Mutat Res. 2000 Oct 31;470(2):177-88. doi: 10.1016/s1383-5718(00)00103-0.
The in vivo mutagenic properties of a 5-nitrofuran, the 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000), already well known in bacteria, was evaluated in lacI 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 lacI 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.
一种5-硝基呋喃，即7-甲氧基-2-硝基萘并[2,1-b]呋喃（R7000），其在细菌中的体内诱变特性已为人熟知，本研究在lacI转基因小鼠（大蓝鼠）中对其进行了评估。测定了经腹腔注射处理的小鼠各个器官中的突变频率，并确定了诱导突变显著的靶器官中诱导突变的性质。结果发现，R7000在小鼠中具有诱变作用，不过，与其他已知诱变化学物质相比，基于每单位质量诱导突变体的数量，R7000在小鼠中的诱变作用似乎远低于在细菌中的作用。受影响最大的器官，小肠、盲肠和结肠器官均属于消化系统。从转基因小鼠小肠中回收的lacI基因中，R7000诱导突变的分布与在大肠杆菌中发现的分布非常相似。小鼠和大肠杆菌在R7000诱导的突变谱方面的差异主要在于单碱基移码与碱基替换的比例。由于R7000诱导的突变似乎出现在干细胞群体中，且干细胞对致癌作用很重要，我们的结果与R7000和其他硝基呋喃可能的致癌作用相符。
