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Cyclophosphamide in Drosophila promotes genes and transposable elements differential expression and mitochondrial dysfunction.
Comparative Biochemistry and Physiology C: Toxicology & Pharmacology ( IF 3.9 ) Pub Date : 2020-01-23 , DOI: 10.1016/j.cbpc.2020.108718
Tailini J R Stoffel 1 , Ana L Segatto 2 , Monica M Silva 2 , Alessandro Prestes 3 , Nilda B V Barbosa 2 , João B T Rocha 2 , Elgion L S Loreto 4
Affiliation  

Cyclophosphamide (CPA) is an alkylating agent used for cancer chemotherapy, organ transplantation, and autoimmune disease treatment. Here, mRNA sequencing and high-resolution respirometry were performed to evaluate the alterations of Drosophila melanogaster gene expression fed with CPA under acute (0.1 mg/mL, for 24 h) and chronic (0.05 mg/mL, for 35 days) treatments. Differential expression analysis was performed using Cufflinks-Cuffdiff, DESeq2, and edgeR software. CPA affected genes are involved in several biological functions, including stress response and immune-related pathways, oxi-reduction and apoptotic processes, and cuticle and vitelline membrane formation. In particular, this is the first report of CPA-induced mitochondrial dysfunction caused by the downregulation of genes involved with mitochondria constituents. CPA treatment also changed the transcription pattern of transposable elements (TEs) from the gypsy and copia superfamilies. The results presented here provided evidence of CPA mitochondrial toxicity mechanisms and that CPA can modify TEs transcription in Drosophila flies.

中文翻译:

果蝇中的环磷酰胺促进基因和转座子差异表达和线粒体功能障碍。

环磷酰胺(CPA)是一种用于癌症化疗,器官移植和自身免疫性疾病治疗的烷基化剂。在这里,进行了mRNA测序和高分辨率呼​​吸测定,以评估在急性(0.1 mg / mL,持续24小时)和慢性(0.05 mg / mL,持续35天)治疗下,CPA喂养的果蝇的果蝇基因表达的变化。使用Cufflinks-Cuffdiff,DESeq2和edgeR软件进行差异表达分析。受CPA影响的基因涉及多种生物学功能,包括应激反应和免疫相关途径,氧化还原和凋亡过程以及表皮和卵黄膜形成。特别是,这是CPA诱导的线粒体功能障碍的首次报道,该线粒体功能障碍是由与线粒体成分有关的基因的下调引起的。CPA治疗还改变了吉普赛人和卡波亚超家族的转座因子(TEs)的转录方式。此处提供的结果提供了CPA线粒体毒性机制的证据,并且CPA可以修饰果蝇果蝇中的TEs转录。
更新日期:2020-01-23
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