Arnaise S, Boeuf H, Buisson J P, Cantat N, Demerseman P, Einhorn J, Lamotte G, Lemelin M, Brimer P A, Perdue S W
Unité de Programmation Moléculaire et Toxicologie Génétique, CNRS LA271, INSERM U163, Institut Pasteur, Paris, France.
Mutagenesis. 1986 May;1(3):217-29. doi: 10.1093/mutage/1.3.217.
The genotoxic activities of 63, 2-nitronaphthofurans and related molecules were examined using two bacterial short-term tests, the Salmonella mammalian microsome assay test or Mutatest, a mutagenesis assay, and/or the SOS Chromotest, an assay for induction of an SOS function in Escherichia coli. Seven compounds were also investigated in the Chinese hamster ovary cells/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) test, a mammalian gene mutation assay. Our main conclusions are the following: (a) Simple empirical rules relating structure to mutagenic activity in the Mutatest can be derived for some of the compounds. In particular, they account for the extremely high Mutagenic Potency of 7-methoxy-1-methyl-2-nitronaphtho[2,1-b]furan (R7372), approximately 2 X 10(6) mutants/nmol on strain TA100. (b) There is a good quantitative correlation between the Mutagenic Potency in the Salmonella/mammalian microsomes assay and the SOS-inducing potency in the SOS Chromotest. This, and previous evidence, suggests strongly that the 2-nitronaphthofurans derivatives are essentially recA and thus probably umuDC-dependent mutagens. (c) Four out of seven compounds tested in the CHO/HGPRT assay gave responses correlated with the bacterial responses. One of them, 7-methoxy-2-nitronaphtho[2,1-b]furan (R7000), is among, or is, the strongest mutagen described for mammalian cells. We briefly discuss the practical and theoretical implications of these results.
使用两种细菌短期试验，即沙门氏菌哺乳动物微粒体试验（亦称突变试验）和诱变试验，以及/或者SOS色变试验（一种用于诱导大肠杆菌中SOS功能的试验），对63种2-硝基萘并呋喃及其相关分子的遗传毒性活性进行了检测。还在中国仓鼠卵巢细胞/次黄嘌呤-鸟嘌呤磷酸核糖转移酶（CHO/HGPRT）试验（一种哺乳动物基因突变试验）中对7种化合物进行了研究。我们的主要结论如下：（a）对于某些化合物，可以得出在突变试验中将结构与诱变活性相关联的简单经验规则。特别是，这些规则解释了7-甲氧基-1-甲基-2-硝基萘并[2,1-b]呋喃（R7372）极高的诱变效力，在TA100菌株上约为2×10⁶个突变体/纳摩尔。（b）沙门氏菌/哺乳动物微粒体试验中的诱变效力与SOS色变试验中的SOS诱导效力之间存在良好的定量相关性。这一点以及先前的证据强烈表明，2-硝基萘并呋喃衍生物本质上是recA依赖性的，因此可能是umuDC依赖性诱变剂。（c）在CHO/HGPRT试验中测试的7种化合物中有4种给出了与细菌试验结果相关的反应。其中之一，7-甲氧基-2-硝基萘并[2,1-b]呋喃（R7000），是已报道的对哺乳动物细胞最强的诱变剂之一，或者就是最强的诱变剂。我们简要讨论了这些结果的实际和理论意义。
