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| Status |
Public on Jun 06, 2018 |
| Title |
Toxicogenomic responses of low level anticancer drug exposures in Daphnia magna |
| Organism |
Daphnia magna |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The use of anticancer drugs in chemotherapy is increasing, leading to growing environmental concentrations of imatinib mesylate (IMA), cisplatinum (CDDP), and etoposide (ETP) in aquatic systems. Previous studies have shown that these anticancer drugs cause DNA damage in the crustacean Daphnia magna at low, environmentally relevant concentrations. To explore the mechanism of action of these compounds and the downstream effects of DNA damage on D. magna growth and development at a sensitive life stage, we exposed neonates to low level concentrations equivalent to those that elicit DNA damage (IMA: 2000 ng/L, ETP: 300 ng/L, CDDP: 10 ng/L) and performed transcriptomic analysis using an RNA-seq approach. RNA sequencing generated 14 million reads per sample, which were aligned to the D. magna genome and assembled, producing approximately 23,000 transcripts per sample. Over 90% of the transcripts showed homology to proteins in GenBank, revealing a high quality transcriptome assembly, although functional annotation was much lower. RT-qPCR was used to identify robust biomarkers and confirmed the downregulation of angiotensin converting enzyme (ACE) involved in neuropeptide regulation across all three anticancer drugs and the down-regulation of DNA topoisomerase II by ETP. RNA-seq analysis also allowed for an in depth exploration of the differential splicing of transcripts revealing that regulation of different gene isoforms predicts potential impacts on translation and protein expression, providing a more meaningful assessment of transcriptomic data. Enrichment analysis and investigation of affected biological processes suggested that the DNA damage caused by ETP and IMA influences cell cycle regulation and GPCR signaling. This dysregulation is likely responsible for effects to neurological system processes and development, and overall growth and development. Our transcriptomic approach provided insight into the mechanisms that respond to DNA damage caused by anticancer drug exposure and generated novel hypotheses on how these chemicals may impact the growth and survival of this ecologically important zooplankton species.
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| Overall design |
Fifteen samples were analyzed in total, including two set of unexposed controls and three replicates per treatment and control, SRA Study:SRP142416 and BioProject:PRJNA453118
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| Contributor(s) |
Russo C, Isidori M, Deaver JA, Poynton HC |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| BioProject |
PRJNA453118 |
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| Submission date |
Jun 05, 2018 |
| Last update date |
Jun 06, 2018 |
| Contact name |
Helen C Poynton |
| E-mail(s) |
helen.poynton@umb.edu
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| Phone |
617-287-7323
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| Organization name |
UMass Boston
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| Department |
School for the Environment
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| Lab |
Poynton Lab
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| Street address |
100 Morrissey Blvd.
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02125 |
| Country |
USA |
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| Platforms (1) |
| GPL21075 |
Illumina HiSeq 2000 (Daphnia magna) |
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| Samples (15)
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| GSM3177134 |
Etoposide, replicate 1 |
| GSM3177135 |
Etoposide, replicate 2 |
| GSM3177136 |
Etoposide, replicate 3 |
| GSM3177137 |
Imatinib mesylate, replicate 1 |
| GSM3177138 |
Imatinib mesylate, replicate 2 |
| GSM3177139 |
Imatinib mesylate, replicate 3 |
| GSM3177140 |
control B, replicate 1 |
| GSM3177141 |
control B, replicate 2 |
| GSM3177142 |
control B, replicate 3 |
| GSM3177143 |
Cisplatinum, replicate 1 |
| GSM3177144 |
Cisplatinum, replicate 2 |
| GSM3177145 |
Cisplatinum, replicate 3 |
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| Relations |
| SRA |
SRP142416 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE115386_Dmagna_cytotoxins_transcriptome.fasta.gz |
13.9 Mb |
(ftp)(http) |
FASTA |
| GSE115386_GEO_cytotoxin_FPKM.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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