GENOTOXIC ACTIVITIES OF 2-NITRONAPHTHOFURANS AND RELATED MOLECULES

GENOTOXIC ACTIVITIES OF 2-NITRONAPHTHOFURANS AND RELATED MOLECULES
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DOI:
10.1093/mutage/1.3.217
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发表时间:
1986-05-01
期刊:
影响因子:
2.7
通讯作者:
HOFNUNG, M
HOFNUNG, M
中科院分区:
医学4区
文献类型:
--
作者:
ARNAISE, S;BOEUF, H;HOFNUNG, M

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63,2 -硝基萘呋喃及其相关分子的基因毒性活性采用两种细菌短期试验,即沙门氏菌哺乳动物微粒体试验或Mutatest(诱变试验)和/或SOS显色试验(在大肠杆菌中诱导SOS功能的试验)来检测。7种化合物还在中国仓鼠卵巢细胞/次黄嘌呤-鸟嘌呤磷酸核糖基转移酶(CHO/HGPRT)试验中进行了研究,这是一种哺乳动物基因突变试验。我们的主要结论如下:(a)对于某些化合物,可以推导出与Mutatest中致突变活性结构有关的简单经验规则。特别是,它们解释了7-甲氧基-1-甲基-2-硝基萘[2,1-b]呋喃(R7372), .apprx极高的诱变效力。2同学们。菌株TA100的106个突变体/nmol。(b)沙门氏菌/哺乳动物微粒体试验的诱变效力与SOS显色试验的诱导效力之间存在良好的定量相关性。这和先前的证据强烈表明,2-硝基萘呋喃衍生物本质上是recA,因此可能是依赖于umudc的诱变剂。(c) CHO/HGPRT试验中检测的7种化合物中有4种的反应与细菌反应相关。其中之一,7-甲氧基-2-硝基萘呋喃(R7000),是已知的针对哺乳动物细胞的最强诱变剂之一。我们简要地讨论了这些结果的实践和理论意义。
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 of 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), .apprx. 2 .times. 106 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.