Quillardet P, Bilger C, Demerseman P, Royer R, Hofnung M
Unit of Molecular Programming and Genetic Toxicology, CNRS UA 271, Institut Pasteur, Paris, France.
Mutat Res. 1988 Feb;204(2):141-7. doi: 10.1016/0165-1218(88)90084-5.
We measured the genotoxic activities in two bacterial tests, the Salmonella/histidine assay (a reverse mutation assay) and the SOS chromotest (an assay for SOS induction in E. coli), of three 2-nitroanthrafurans: 2-nitroanthra[1,2-b]furan (R-7688), the isomeric compound 2-nitroanthra[2,1-b]furan (R-7686) and its 8-methoxylated derivative (R-7707). Their genotoxic activities were compared to that of 7-methoxy-2-nitronaphtho[2,1-b]furan (R-7000) which has been studied in previous works (Arnaise et al., 1986). We found that: (1) for all three 2-nitroanthrafurans, as generally observed for other 2-nitrofuran derivatives, the responses were correlated in the 2 tests and were decreased in the presence of an 'activating mixture' and in nitroreductase-deficient strains; (2) in contrast to what is usually observed with other 2-nitrofuran derivatives for which methoxylation increases genotoxic activity, the genotoxic activity of the methoxylated 2-nitroanthrafuran (R-7707) was comparable and may be even lower than that of the unsubstituted 2-nitroanthrafuran (R-7686); (3) the addition of a third ring that leads from 2-nitronaphthofurans to 2-nitroanthrafurans increased slightly the genotoxic activity of these compounds; (4) compounds with the oxygen heteroatom outside the 'bay region', R-7686 and R-7707, gave higher responses than their isomers with the oxygen heteroatom within the 'bay region', R-7688.
我们在两项细菌试验中测定了三种2-硝基蒽呋喃的遗传毒性活性，这两项试验分别是沙门氏菌/组氨酸试验（一种回复突变试验）和SOS色变试验（一种用于检测大肠杆菌中SOS诱导的试验），这三种2-硝基蒽呋喃分别是：2-硝基蒽并[1,2-b]呋喃（R-7688）、同分异构化合物2-硝基蒽并[2,1-b]呋喃（R-7686）及其8-甲氧基化衍生物（R-7707）。将它们的遗传毒性活性与先前研究（阿尔奈斯等人，1986年）中已研究过的7-甲氧基-2-硝基萘并[2,1-b]呋喃（R-7000）的遗传毒性活性进行了比较。我们发现：（1）对于所有三种2-硝基蒽呋喃，正如通常在其他2-硝基呋喃衍生物中观察到的那样，这两项试验中的反应具有相关性，并且在存在“活化混合物”和硝基还原酶缺陷菌株的情况下反应降低；（2）与通常在其他2-硝基呋喃衍生物中观察到的甲氧基化会增加遗传毒性活性相反，甲氧基化的2-硝基蒽呋喃（R-7707）的遗传毒性活性相当，甚至可能低于未取代的2-硝基蒽呋喃（R-7686）；（3）从2-硝基萘并呋喃到2-硝基蒽并呋喃增加的第三个环略微增加了这些化合物的遗传毒性活性；（4）氧杂原子在“湾区”之外的化合物R-7686和R-7707，比其氧杂原子在“湾区”之内的异构体R-7688给出了更高的反应。
