Effects of hydroxyurea on CNV induction in the mouse germline
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PROVIDER: PRJNA472574 | ENA |
REPOSITORIES: ENA
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Project description:We examined the effects of hydroxyurea (HU) treatment on germline copy number variants (CNVs) in vivo in male mice. Several trials of HU administration were performed by oral gavage and subcutaneous pump, with CNVs characterized in C57BL/6 x C3H/HeJ hybrid mouse offspring by microarray and mate-pair sequencing. This accession contains the Nimblegen aCGH microarray data from mice treated by oral gavage or by subcutaneous pump.
2019-05-08 | GSE114754 | GEO
Project description:Copy number variants (CNVs) are important in genome variation and genetic disease, with new mutations arising frequently in the germline and somatic cells. Replication stress caused by aphidicolin and hydroxyurea (HU) is a potent inducer of de novo CNVs in cultured mammalian cells. HU is used extensively for long-term management of sickle cell disease. Here, we examined the effects of HU treatment on germline CNVs in vivo in male mice to explore whether replication stress can act as a CNV mutagen in germline mitotic divisions as in cultured cells and whether this would support a concern for increased CNV mutations in offspring of men treated with HU. Several trials of HU administration were performed by oral gavage and subcutaneous pump, with CNVs characterized in C57BL/6 x C3H/HeJ hybrid mouse offspring by microarray and mate-pair sequencing. HU had a short half-life of ~14 min and a narrow dose window over which studies could be performed while maintaining fertility. Tissue histopathology and reticulocyte micronucleus assays verified that doses had a substantial tissue and genetic toxicity. CNVs were readily detected in offspring that originated in both paternal and maternal mouse strains, as de novo and inherited events. However, HU did not increase CNV formation above baseline levels. These results reveal a high rate of CNV mutagenesis in the mouse germline but do not support the hypothesis that HU would increase CNV formation during mammalian spermatogenesis, perhaps due to highly toxic effects on sperm development or experimental variables related to HU pharmacology in mice. Environ. Mol. Mutagen. 59:698-714, 2018. © 2018 Wiley Periodicals, Inc.
| S-EPMC7275641 | biostudies-literature
Project description:We hypothesized that miRNA regulation may be invloved in hydroxyurea-mediated fetal hemoglobin induction. Microarray analysis was utilized as an initial screening tool to determine differential miRNA expression in CD71+ erythroid cells comparing cells from control individuals without sickle cell anemia to patients with sickle cell anemia prior to treatment with hydroxyurea and patients receiving the maximum tolerated dose (MTD) of hydroxurea.
2011-11-21 | GSE32035 | GEO
Project description:We hypothesized that miRNA regulation may be invloved in hydroxyurea-mediated fetal hemoglobin induction. Microarray analysis was utilized as an initial screening tool to determine differential miRNA expression in CD71+ erythroid cells comparing cells from control individuals without sickle cell anemia to patients with sickle cell anemia prior to treatment with hydroxyurea and patients receiving the maximum tolerated dose (MTD) of hydroxurea. CD71+ cells were isolated from whole blood of control individuals (n=2), pediatric patients without hydroxyurea treatment (n=3) and pediatric patients at hydroxyurea MTD (n=3). All 8 samples were analyzed for miRNA expression.
2011-11-21 | E-GEOD-32035 | biostudies-arrayexpress
Project description:Copy number analysis of Affymetrix GW6.0 SNP/CNV arrays was performed for 7 tumours (4 adrenocortical carcinomas, 2 rhabdomyosarcoma and 1 extra-renal rhabdoid tumour) derived from individuals with germline p53-mutations. Affymetrix CNV/SNP arrays were performed according to the manufacturer's directions on DNA extracted from fresh frozen tumour samples
2012-01-19 | E-GEOD-34323 | biostudies-arrayexpress
Project description:Hydroxyurea (HU) is thought to primarily target ribonucleotide reductase (RNR), therefore inhibiting the conversion of rNTPs into dNTPs and slowing DNA replication. To understand how Bacillus subtilis responds to HU stress, we performed RNA-seq and Tn-seq. We obtained genes with fitness defects following hydroxyurea treatment over 3 growth periods.
2021-03-29 | GSE169564 | GEO
Project description:Multicenter Study of Hydroxyurea (MSH)
| PRJNA701326 | ENA