• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Mutation Research, A. Reviews in Genetic Toxicology >Substituent effects on the genotoxicity of 4-nitrostilbene derivatives
【24h】

Substituent effects on the genotoxicity of 4-nitrostilbene derivatives

机译：取代基对4-硝基二苯乙烯衍生物的遗传毒性的影响

获取原文
获取原文并翻译 | 示例
       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

4-Nitrostilbcne and twelve of its derivatives (eleven E-stilbcnes and two Z-stilbcnes) were examined for possible quantitative structure-activity relationships of their in vitro and in vivo genotoxicity. Relative mutagenicity was studied with and without S9 activation in Salmonella strains TA98 and TAKK), as well as in the nitroreductase deficient strains TA98/NR and TA100/NR. Chromosomal aberrations in the hone-marrow cells of mice following intraporitoncal administration of the nitrostilbenes wereobserved as an indicator of in vivo genotoxicity. All of the compounds were active in TA98 and TA100 without S9 activation, with the exception of 4-amino-4'-nitrostilbene in TAIOO. Mutagenic activity was greatly reduced or eliminated in the NR strains, which is consistent with metabolic activation of the compounds by bacterial rcduetase. The presence of S9 lowered the activity of most of the nitrostilbencs presumedly by enzymatic detoxication. Hammet values of substitucnts, partition coefficients and frontier orbital energies (E_(LUMO) and E_(HOMO)) were studied for correlations with mutagenicity of the eleven E-stilbenes, Correlations could be established between mutagenicity in TA98 without S9 activation and the Hammet values. The same mutagenicity could also be correlated to E_(LUMO). Rationales for these correlations include the concept that electron-withdrawing groups which lower E_(LUMO) should facilitate the reduction of the nitro group, leading to the proximate mutagen hydroxylamine. The correlations arc also explained by the concept that electron-withdrawing groups should help stabilize the hydroxylamine intermediate and make the ultimate mutagenic species, the nitrenium ions, more reactive toward DNA. The relationship between mutagenicity and electronic effects of substituent groups found in vitro could not be extended to the in vivo results. However, except for the dinitrostilbcncs, where insolubility prevented their testing, all the nitrostilbenes produced a statistically significant increase in chromosomal aberrations compared to the negative solvent control.
机译：检查了4-硝基stilbcne及其十二种衍生物（十一种E-stilbcnes和两个Z-stilbcnes）在体外和体内遗传毒性方面可能的定量构效关系。在沙门氏菌菌株TA98和TAKK，以及硝基还原酶缺陷菌株TA98 / NR和TA100 / NR中，研究了有和没有S9激活的相对诱变性。观察到腹膜内施用亚硝基苯磺酰苯之后，小鼠的骨髓细胞中的染色体畸变是体内遗传毒性的指标。除TA100中的4-氨基-4'-亚硝基二苯乙烯外，所有化合物均在没有S9活化的情况下在TA98和TA100中具有活性。在NR菌株中，诱变活性大大降低或消除，这与细菌rcduetase对化合物的代谢活化相一致。 S9的存在降低了大多数亚硝基苯的活性，推测是由于酶促解毒作用。研究了11种E-芪的致突变性与取代基，分配系数和前沿轨道能量（E_（LUMO）和E_（HOMO））的Hammet值之间的相关性，可以建立没有激活S9的TA98的致突变性与Hammet值之间的相关性。 。相同的诱变性也可以与E_（LUMO）相关。这些相关性的理由包括降低E_（LUMO）的吸电子基团应促进硝基的还原，从而导致邻近的诱变羟胺的概念。这种相关性还可以用吸电子基团应有助于稳定羟胺中间体并使最终诱变的物种（氮离子）对DNA更具反应性这一概念来解释。体外发现的诱变性与取代基电子效应之间的关系不能扩展到体内结果。但是，除了不溶性阻止其测试的二亚硝基苯并噻吩以外，与负溶剂对照相比，所有亚硝基苯酚均在统计学上显着增加了染色体畸变。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号