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利用黑腹果蝇中的体突变和重组试验对选择性 5-羟色胺再摄取抑制剂的遗传毒性评估。

Genotoxic evaluation of selective serotonin-reuptake inhibitors by use of the somatic mutation and recombination test in Drosophila melanogaster.

机构信息

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

出版信息

Mutat Res. 2012 Oct 9;748(1-2):17-20. doi: 10.1016/j.mrgentox.2012.06.004. Epub 2012 Jun 29.

Abstract

This study evaluated different concentrations of selective serotonin-reuptake inhibitors (citalopram and sertraline) for genotoxicity by use of the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Three-day-old larvae, trans-heterozygous for the multiple wing hairs (mwh) and flare (flr³) genes were treated with these two compounds. Two recessive markers were located on the left arm of chromosome 3, i.e. 'multiple wing hairs' (mwh) in map position 0.3 and 'flare-3' (flr³) at 38.8, while the centromere was located in position 47.7. SMART is based on the loss of heterozygosity, which may occur through various mechanisms, such as mitotic recombination, mutation, deletion, half-translocation, chromosome loss, and non-disjunction. Genetic changes occurring in somatic cells of the wing's imaginal discs, cause the formation of mutant clones on the wing blade. The results of this study show that citalopram had a genotoxic effect in the Drosophila SMART. Sertraline, however, did not show any genotoxic effect in balancer heterozygous wings. This study concluded that more information is needed to be certain regarding the mutagenic effects of sertraline.

摘要

本研究通过黑腹果蝇的体突变和重组测试(SMART)评估了不同浓度的选择性 5-羟色胺再摄取抑制剂(西酞普兰和舍曲林)的遗传毒性。用这两种化合物处理 3 天大的幼虫,它们是多个翅毛(mwh)和耀斑(flr³)基因的反式杂合子。两个隐性标记位于染色体 3 的左臂上,即 0.3 位置的“多个翅毛”(mwh)和 38.8 位置的“耀斑-3”(flr³),而着丝粒位于 47.7 位置。SMART 基于杂合性丢失,这可能通过多种机制发生,例如有丝分裂重组、突变、缺失、半易位、染色体丢失和不分离。发生在翅膀的 imaginal 盘的体细胞中的遗传变化导致在翅膀上形成突变克隆。本研究的结果表明,西酞普兰在 Drosophila SMART 中具有遗传毒性作用。然而,舍曲林在平衡杂合翅膀中没有显示出任何遗传毒性作用。本研究得出结论,需要更多信息来确定舍曲林的诱变作用。

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