ArticleToxicological sciences : an official journal of the Society of Toxicology2010
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 46 citations in OpenAlex.
- The Roles of Moonlighting Nicotinamide Mononucleotide Adenylyl Transferases in Cell Physiology.International journal of molecular sciences · 2025Review
- Identification of putative calorie restriction mimetics using mammalian gene expression profiles.Open biology · 2020Article
- Induction of hemangiosarcoma in mice after chronic treatment with S1P-modulator siponimod and its lack of relevance to rat and human.Archives of toxicology · 2018Article
- Prior knowledge-based approach for associating contaminants with biological effects: A case study in the St. Croix River basin, MN, WI, USA.Environmental pollution (Barking, Essex : 1987) · 2017Article
- Metastatic hemangiosarcoma of the liver in a young rat.Journal of toxicologic pathology · 2017Article
- Pathobiology of Hemangiosarcoma in Dogs: Research Advances and Future Perspectives.Veterinary sciences · 2015Review
- Reverse causal reasoning: applying qualitative causal knowledge to the interpretation of high-throughput data.BMC bioinformatics · 2013Article
- Aberrations in Angiogenic Signaling and MYC Amplifications are Distinguishing Features of Angiosarcoma.Angiology: open access · 2013Article
- Assessment of network perturbation amplitudes by applying high-throughput data to causal biological networks.BMC systems biology · 2012Article
- Assessing statistical significance in causal graphs.BMC bioinformatics · 2012Article
- Genome-scale technology driven advances to research into normal and malignant haematopoiesis.Scientifica · 2012Review
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- A cross-species analysis method to analyze animal models' similarity to human's disease state.BMC systems biology · 2012Article
- Construction of a computable cell proliferation network focused on non-diseased lung cells.BMC systems biology · 2011Article
- Nicotinamide mononucleotide adenylyltransferase is a stress response protein regulated by the heat shock factor/hypoxia-inducible factor 1alpha pathway.The Journal of biological chemistry · 2011Article
- Causal reasoning identifies mechanisms of sensitivity for a novel AKT kinase inhibitor, GSK690693.BMC genomics · 2010Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To understand the molecular mechanisms underlying compound-induced hemangiosarcomas in mice, and therefore, their human relevance, a systems biology approach was undertaken using transcriptomics and Causal Network Modeling from mice treated with 2-butoxyethanol (2-BE). 2-BE is a hemolytic agent that induces hemangiosarcomas in mice. We hypothesized that the hemolysis induced by 2-BE would result in local tissue hypoxia, a well-documented trigger for endothelial cell proliferation leading to hemangiosarcoma. Gene expression data from bone marrow (BM), liver, and spleen of mice exposed to a single dose (4 h) or seven daily doses of 2-BE were used to develop a mechanistic model of hemangiosarcoma. The resulting mechanistic model confirms previous work proposing that 2-BE induces macrophage activation and inflammation in the liver. In addition, the model supports local tissue hypoxia in the liver and spleen, coupled with increased erythropoeitin signaling and erythropoiesis in the spleen and BM, and suppression of mechanisms that contribute to genomic stability, events that could be contributing factors to hemangiosarcoma formation. Finally, an immunohistochemistry method (Hypoxyprobe) demonstrated that tissue hypoxia was present in the spleen and BM. Together, the results of this study identify molecular mechanisms that initiate hemangiosarcoma, a key step in understanding safety concerns that can impact drug decision processes, and identified hypoxia as a possible contributing factor for 2-BE-induced hemangiosarcoma in mice.
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