参考DNA结合差异评估拓扑异构酶II中毒引起的全局基因表达变化。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2022-03-01 DOI:10.2174/1874467215666220301115946
Malek Zihlif, Daniel R Catchpoole, Bernard W Stewart, Laurence P G Wakelin
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引用次数: 0

摘要

背景DNA相互作用药物诱导的基因表达改变模式可能提供有关这些药物引起的生物影响的见解。方法利用具有6000个特征的cDNA微阵列,比较了拓扑异构酶II毒素(阿霉素、米托蒽醌和安沙林)和三种吖啶酰胺(N-[2-(二甲基氨基)乙基]酸-4-甲酰胺及其9氨基和5甲基砜衍生物(DACA、9-氨基-DACA和AS-DACA))。使用CEM细胞,所有研究都涉及暴露于5倍IC50浓度24小时后的cDNA群体的分析,一式三份。结果在化合物之间比较了表现出大于4倍变化的表达改变的基因。除9-氨基DACA外,所有化合物都具有相似的效果,即通过表达减少鉴定的基因数量超过显示表达增强的数量的至少3倍。无监督的分级聚类证实了表现出表达改变的基因的试剂特异性反应特征。表达减少的基因亚群在拓扑异构酶毒物中以及在DACA和AS-DACA之间是常见的。对基因本体数据库的询问表明,对于所有测试的化合物,表现出表达改变的基因被鉴定为具有转录、防御反应、磷酸化和蛋白质分解代谢的调节。就这些和其他本体组而言,分层聚类表明,米托蒽醌、DACA、阿霉素和AS-DACA下调的基因与amsacrine和9-氨基-DACA作为异常值的关系最为密切。结论这些结果可能与目前对最终致命损伤细胞中基因表达改变的理解、目前对药物诱导的基因组损伤之间序列特异性变化的了解及其DNA结合特征有关。
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Withdrawn: Variations in Altered Global Gene Expression caused by Topoisomerase II Poisons Assessed with Reference to Differences in DNA Binding

The article has been withdrawn at the request of the authors of the journal Current Molecular Pharmacology.

Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.

The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php.

Bentham science disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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