Project description:Time series of urine samples collected from male and female mice after exposure to 6PPD and 6PPDQ. Analyzed with LC-DDA-MS/MS. Rerun of tissue samples from pregnant mice exposed to 6PPD and 6PPDQ.
Project description:Acrylamide, a high-production-volume chemical and food contaminant in baked and fried carbohydrate-rich foods has been classified as a “Group 2A carcinogen” (probable human carcinogen) by the IARC. The carcinogenicity of acrylamide is attributed to its well-recognized genotoxicity; however, evidence suggests that acrylamide may also induce non-genotoxic alterations. In the present study female B6C3F1 mice were exposed to 0.70mM acrylamide in drinking water for 28 days and genotoxic and transcriptomic effects were investigated in the lung, a target organ for acrylamide carcinogenicity in mice, and the liver, a non-target organ. Acrylamide exposure resulted in a dose-dependent formation of N7-(2-carbamoyl-2-hydroxyethyl)guanine and N3-(2-carbamoyl-2-hydroxyethyl)adenine in lung and liver DNA at the similar levels. In contrast, whole genome gene expression profiles in the lungs and livers revealed the tissue-specific gene expression alterations. By using a SurePrint G3 Mouse Gene Expression v2 8x60K Microarray Kit (Agilent Technologies), we identified 123 and 363 genes that were found to be differentially expressed in the lungs and livers of acrylamide-treated mice; however, only 5 genes were in common between the organs. A detailed analysis of differentially expressed genes revealed that the major difference in the effect of acrylamide on the transcriptome in the lungs and livers was related to a different trend of gene expression changes. In the lungs, acrylamide exposure caused an inhibition of gene expression (54 up-regulated and 69 down-regulated genes), whereas the opposite effect, characterized by twice the number of up-regulated as compare to down-regulated genes (245 up-regulated and 118 down-regulated), was found in the livers of exposed mice.
Project description:Transcriptional profiling of mouse lung tissue comparing control vs exposure to different carbon nanotubes. The aim was to determine if the physico-chemical properties influence the genotoxic, inflammatory and pro-fibrotic responses.
Project description:To identify the molecular impact of SPIO nanoparticle inhalation exposure on lung tissue. Transcriptional responses were measured by global microarray analysis of mouse lung.
Project description:The goal of this project is to identify metabolites released from subcutaneous adipose tissue due to light exposure that regulate systemic metabolism. We found that histidine levels increased by 8 days of blue light exposure, both in the treated subcutaneous adipose tissue and in circulation. Additionally, blue light-induced circulating histidine levels were not affected by the central blockade of histidine decarboxylase activity using FMH (Fluoromethylhistidine) in the hypothalamus. The details are described in the Summary Excel file.
Project description:The processes involved in the adaptation of animals to environmental factors such as chemicals have not yet been fully elucidated. We focused on the adaptive potential of the mouse liver against hepatotoxic chemical-induced injury. We used microarrays to determine genes with adaptive transcriptional regulation against ethylbenzene, hepatotoxic chemical, on multistep-exposure.
Project description:The World Health Organization has recognized testicular function with temperature dependence. Testicular heat exposure caused by occupational factors, lifestyle and clinical disease, etc., can lead to different degrees of reproductive obstacles. The aim of this study is to reveal the transcriptional regulatory network and their potential crucial roles in testicular heat exposure. After passing quality control, the high throughput sequencing data of mouse testicular tissue for scrotum heat exposure and control group were carried out various analyses including differentially expressed transcriptome exploration, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and network regulation. Differential transcriptome expression analysis revealed that 279 miRNAs (138 upregulation and 141 downregulation) were identified as significant differential expression in the mouse testicular tissue of heat exposure compared with control group using the cut-off of log2fold change >= 0.585, p value <= 0.05 and q value <= 1.00. This research provides high throughput sequencing data of transcriptome in testicular heat exposure model and lays the foundation for further study on the miRNA in male reproductive diseases related to elevated testicular temperature.
Project description:Phosgene is a lung damaging chemical warfare agent which can cause death by the inhalation route. In this study the inflammatory response to phosgene was mapped over a 96h time-course using a custom microarray in the Balb/c mouse. Three groups of six mice were exposed to phosgene and a three groups exposed to an air only control. Following exposure mice were culled at 6 timepoints (1, 4, 7, 24, 48 and 96h). RNA was extracted and run on the custom array.
Project description:The developing epigenome changes rapidly, potentially making it more sensitive to toxicant exposures. DNA modifications, including methylation and hydroxymethylation, are important parts of the epigenome that may be affected by environmental exposures. However, most studies do not differentiate between these two DNA modifications, possibly masking significant effects. To investigate the relationship between DNA hydroxymethylation and developmental exposure to common contaminants, a collaborative, NIEHS-sponsored consortium, TaRGET II, initiated longitudinal mouse studies of developmental exposure to human-relevant levels of the phthalate plasticizer di(2-ethylhexyl) phthalate (DEHP), and the metal lead (Pb). Exposures to 25 mg DEHP/kg of food (approximately 5 mg DEHP/kg body weight) or 32 ppm Pb-acetate in drinking water were administered to nulliparous adult female mice. Exposure began 2 weeks before breeding, and continued throughout pregnancy and lactation, until offspring were 21 days old. At 5 months, perinatally exposed offspring blood and cortex tissue were collected, for a total of 25 male mice and 17 female mice (n=5-7 per tissue and exposure). DNA was extracted and hydroxymethylation was measured using hydroxymethylated DNA immunoprecipitation sequencing (hMeDIP-seq). Differential peak and pathway analysis was conducted comparing across exposure groups, tissue types, and animal sex, using an FDR cutoff of 0.15. DEHP-exposed females had two genomic regions with lower hydroxymethylation in blood and no differences in cortex hydroxymethylation. For DEHP-exposed males, ten regions in blood (six higher and four lower) and 246 regions (242 higher and four lower) and four pathways in cortex were identified. Pb-exposed females had no statistically significant differences in blood or cortex hydroxymethylation compared to controls. Pb-exposed males, however, had 385 regions (all higher) and six pathways altered in cortex, but no differential hydroxymethylation was identified in blood. Overall, perinatal exposure to human-relevant levels of two common toxicants showed differences in DNA hydroxymethylation specific to sex, exposure type, and tissue, but male cortex was most susceptible to hydroxymethylation differences by exposure. Future assessments should focus on understanding if these findings indicate potential biomarkers of exposure or are related to functional long-term health effects.