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应用黑腹果蝇体细胞突变和重组试验分析氯胺酮和罗库溴铵的遗传毒性活性。

Analysis of genotoxic activity of ketamine and rocuronium bromide using the somatic mutation and recombination test in Drosophila melanogaster.

机构信息

Department of Biology, Faculty of Arts and Sciences, Erzincan University, 24100 Erzincan, Turkey.

Department of Biology, Faculty of Arts and Sciences, Erzincan University, 24100 Erzincan, Turkey.

出版信息

Environ Toxicol Pharmacol. 2015 Mar;39(2):628-34. doi: 10.1016/j.etap.2014.12.010. Epub 2014 Dec 27.

Abstract

The present study evaluated the mutagenic and recombinogenic effects of two commonly used anesthetic agents, ketamine and rocuronium bromide, in medicine using the wing somatic mutation and recombination test (SMART) in Drosophila. The standard (ST) cross and the high-bioactivation (HB) cross with high sensitivity to procarcinogens and promutagens were used. The SMART test is based on the loss of heterozygosity, which occurs via various mechanisms, such as chromosome loss and deletion, half-translocation, mitotic recombination, mutation, and non-disjunction. Genetic alterations occurring in the somatic cells of the wing's imaginal discs result in mutant clones in the wing blade. Three-day-old trans-heterozygous larvae with two recessive markers, multiple wing hairs (mwh) and flare (flr(3)), were treated with ketamine and rocuronium bromide. Analysis of the ST cross indicated that ketamine exhibited genotoxicity activity and that this activity was particularly dependent on homologous mitotic recombination at concentrations of 250 μg/ml and above. Rocuronium bromide did not exert mutagenic and/or recombinogenic effects. In the HB cross, ketamine at a concentration of 1000 μg/ml and rocuronium bromide at all concentrations, with the exception of 250 μg/ml (inconclusive), exerted genotoxic effects, which could also be associated with the increase in mitotic recombination.

摘要

本研究使用果蝇的翅体突变和重组测试(SMART)评估了两种常用麻醉剂,氯胺酮和罗库溴铵,在医学上的诱变和重组效应。使用标准(ST)交叉和高生物活化(HB)交叉,对前致癌物和促突变剂具有高灵敏度。SMART 测试基于杂合性丢失,其通过各种机制发生,例如染色体丢失和缺失、半易位、有丝分裂重组、突变和不分离。在翅的胚盘体细胞中发生的遗传改变导致翅片中出现突变克隆。用氯胺酮和罗库溴铵处理具有两个隐性标记(多毛 mwh 和 flare flr(3))的三天大的异合子幼虫。ST 交叉分析表明,氯胺酮具有遗传毒性活性,这种活性特别依赖于同源有丝分裂重组,在 250μg/ml 及以上浓度下。罗库溴铵没有表现出诱变和/或重组效应。在 HB 交叉中,氯胺酮在 1000μg/ml 的浓度下,以及除了 250μg/ml(不确定)的所有浓度下的罗库溴铵,都表现出遗传毒性作用,这也可能与有丝分裂重组的增加有关。

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