Although various mechanisms have been inferred for combinatorial actions of multiple carcinogens, these mechanisms have not been well demonstrated in experimental carcinogenesis models. We evaluated mammary carcinogenesis initiated by combined exposure to various doses of radiation and chemical carcinogens. Female rats at 7 weeks of age were -irradiated (0.22 Gy) and/or exposed to 1-methyl-1-nitrosourea (20 or 40 mg/kg, single intraperitoneal injection) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (40 mg/kg/day by gavage for 10 days) and were observed until 50 weeks of age. The incidence of mammary carcinoma increased steadily as a function of radiation dose in the absence of chemicals; mathematical analysis supported an additive increase when radiation was combined with a chemical carcinogen, irrespective of the chemical species and its dose. Hras mutations were characteristic of carcinomas that developed after chemical carcinogen treatments and were overrepresented in carcinomas induced by the combination of radiation and MNU (but not PhIP), indicating an interaction of radiation and MNU at the level of initiation. The expression profiles of seven classifier genes, previously shown to distinguish two classes of rat mammary carcinomas, categorized almost all examined carcinomas that developed after individual or combined treatments with radiation (1 Gy) and chemicals as belonging to a single class; more comprehensive screening using microarrays and a separate test sample set failed to identify differences in gene expression profiles among these carcinomas. These results suggest that a complex, multilevel interaction underlies the combinatorial action of radiation and chemical carcinogens in the experimental model.
Molecular characterization of cancer reveals interactions between ionizing radiation and chemicals on rat mammary carcinogenesis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part, Cell line
View SamplesPDX1 binds and regulates numerous genes involved in human pancreatic development but also binds hepatic genes
No associated publication
Cell line
View SamplesPseudomonas aeruginosa chronically colonizes the lungs of individuals with CF, where it reaches high cell densities and produces a battery of virulence factors. Upon infection, a single strain of P. aeruginosa can colonize an individuals lungs throughout his or her lifetime. To understand the evolution of P. aeruginosa during chronic lung infection, we conducted both genotypic and phenotypic analyses on clinical isogenic strains obtained from the lungs of three different individuals with CF. These strains were isolated over a period of approximately ten years and possess phenotypes that are commonly observed in isolates from the CF lung, such as the antibiotic resistant dwarf and mucoid phenotypes. Microarray analyses were carried out on isolates grown in a chemically defined medium that mimics the nutritional environment of the CF lung, synthetic CF sputum medium (SCFM).
Parallel evolution in Pseudomonas aeruginosa over 39,000 generations in vivo.
Time
View SamplesSelective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressant drugs in pregnant women. Given that SSRIs can cross the placental and blood-brain barriers, these drugs potentially affect serotonergic neurotransmission and neurodevelopment in the fetus. Although no gross SSRI-related teratogenic effect has been reported, infants born following prenatal exposure to SSRIs have a higher risk for various behavioral abnormalities. Therefore, we examined the effects of prenatal fluoxetine, the most commonly prescribed SSRI, on social and cognitive behavior in mice. Intriguingly, chronic in utero fluoxetine treatment impaired working memory and social novelty recognition in adult males with augmented spontaneous inhibitory synaptic transmission onto the layer 5 pyramidal neurons in the medial prefrontal cortex (mPFC). Moreover, fast-spiking interneurons in the layer 5 mPFC exhibited enhanced basal intrinsic excitability, augmented serotonin-induced neuronal excitability, and increased inhibitory synaptic transmission onto the layer 5 pyramidal neurons due to augmented 5-HT2A receptor (5-HT2AR) signaling. More importantly, the observed behavioral deficits of in utero fluoxetine-treated mice could be reversed by acute systemic application of 5-HT2AR antagonist. Taken together, our findings support the notion that alterations in serotonin-mediated inhibitory neuronal modulation result in reduced cortical network activities and cognitive impairment following prenatal exposure to SSRIs.
No associated publication
Sex, Specimen part, Treatment
View Samplesp53 is critically important in preventing oncogenesis but its role in non-cancer biology remains unclear. Macrophages exist as two subtypes (M1 and M2). Nutlin-3a (p53 activator) inhibits M2 gene expression and phenotype. p53 acts by suppressing transcription of c-Myc and thence regulates expression of a subset of M2 markers. This work has implications for our understanding of the mechanisms that regulate plasticity of macrophages in health and disease.
A unique role for p53 in the regulation of M2 macrophage polarization.
Specimen part, Treatment
View SamplesTotal 23 samples were derived from [1] HUVEC treated in the absence (0h) or presence of hypoxia (1, 2, 4, 8, 12, and 24 hrs) to determine hypoxia-regulated gene in endothelial cells, [2] control siRNA or HIF1 siRNA transfected HUVEC cells treated in the absence or presence of hypoxia, [3] control siRNA or KDM3A siRNA transfected HUVEC cells treated in the absence or presence of hypoxia, [4] ChIP-seq data for HIF1 binding sites and histone modifications under normoxia and hypoxia in endothelial cells.
Dynamic change of chromatin conformation in response to hypoxia enhances the expression of GLUT3 (SLC2A3) by cooperative interaction of hypoxia-inducible factor 1 and KDM3A.
Cell line, Treatment
View SamplesIn order to clarify the downstream target genes of SPAG4, we performed knockdown of SPAG4 using siRNA both under normoxia and hypoxia.
Sperm-associated antigen 4, a novel hypoxia-inducible factor 1 target, regulates cytokinesis, and its expression correlates with the prognosis of renal cell carcinoma.
Cell line
View SamplesThe functional activity of TRPM7 is essential for cell viability and growth, and its expression is up-regulated in certain pathological conditions. In order to assess the effects of TRPM7 activity on cellular gene expression, inducible HEK293 cell-lines harboring the wild-type mouse TRPM7 and a mutant lacking the kinase domain were established.
Alteration of the transcriptional profile of human embryonic kidney cells by transient overexpression of mouse TRPM7 channels.
Cell line
View SamplesThe Arabidopsis thaliana NAC domain transcription factor, VASCULAR-RELATED NAC-DOMAIN7 (VND7), acts as a key regulator of xylem vessel differentiation. In order to identify direct target genes of VND7, we performed global transcriptome analysis using Arabidopsis transgenic lines in which VND7 activity could be induced post-translationally. This analysis identified 63 putative direct target genes of VND7, which encode a broad range of proteins, such as transcription factors, IRREGULAR XYLEM proteins and proteolytic enzymes, known to be closely associated with xylem vessel formation. Recombinant VND7 protein binds to several promoter sequences present in candidate direct target genes: specifically, in the promoter of XYLEM CYSTEINE PEPTIDASE1, two distinct regions were demonstrated to be responsible for VND7 binding. We also found that expression of VND7 restores secondary cell wall formation in the fiber cells of inflorescence stems of nst1nst3 double mutants, as well as expression of NAC SECONDARY WALL THICKENING PROMOTING FACTOR3 (NST3, however, the vessel-type secondary wall deposition was observed only as a result of VND7 expression. These findings indicated that VND7 upregulates, directly and/or indirectly, many genes involved in a wide range of processes in xylem vessel differentiation, and that its target genes are partially different from those of NSTs.
VASCULAR-RELATED NAC-DOMAIN7 directly regulates the expression of a broad range of genes for xylem vessel formation.
Age, Specimen part, Treatment
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