Bisphenol A-Induced Ovotoxicity Involves DNA Damage Induction to Which the Ovary Mounts a Protective Response Indicated by Increased Expression of Proteins Involved in DNA Repair and Xenobiotic Biotransformation
Bisphenol A (BPA) is an endocrine disrupting chemical with ubiquitous human exposure. BPA causes primordial follicle loss and DNA damage in germ cells, thus we hypothesized that BPA induces ovarian DNA damage, thereby precipitating follicle loss. We also anticipated that the ovary activates DNA repair and xenobiotic biotransformation to minimize oocyte damage and/or, activate cell death signaling to deplete follicles. Postnatal day 4 F344 rat ovaries were cultured in medium containing vehicle control (1% dimethylsulfoxide [DMSO]) ± BPA (440 µM) for 2–8 days. BPA reduced (P < 0.05) small primary, large...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Ganesan, S., Keating, A. F. Tags: Bisphenol a Exposure Causes DNA Damage in Ovaries Source Type: research
Gene Expression Profiling Identifies Cell Proliferation and Inflammation as the Predominant Pathways Regulated by Aryl Hydrocarbon Receptor in Primary Human Fetal Lung Cells Exposed to Hyperoxia
Exposure to hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. We observed that aryl hydrocarbon receptor (AhR) signaling protects newborn mice and primary fetal human pulmonary microvascular endothelial cells (HPMECs) against hyperoxic injury. Additionally, a recent genome-wide transcriptome study in a newborn mouse model of BPD identified AhR as a key regulator of hyperoxia-induced gene dysregulation. Whether the AhR similarly deregulates genes in HPMEC is unknown. Therefore, the objective of this study was to characterize transcriptome level gene expression profile in AhR-...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Shivanna, B., Maity, S., Zhang, S., Patel, A., Jiang, W., Wang, L., Welty, S. E., Belmont, J., Coarfa, C., Moorthy, B. Tags: Aryl Hydrocarbon Receptor-Mediated Inflammation and Cell Proliferation in Lung Cells Exposed to High Oxygen Source Type: research
Bisphenol A Impairs Mature Sperm Functions by a CatSper-Relevant Mechanism
In conclusion, both in vivo administration and in vitro application of BPA impair mature sperm functions by a CatSper-relevant mechanism. (Source: Toxicological Sciences)
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Wang, H.-F., Liu, M., Li, N., Luo, T., Zheng, L.-P., Zeng, X.-H. Tags: Sperm Function Altered by Bisphenol a Exposure Source Type: research
Effects of Polyamidoamine Dendrimers on a 3-D Neurosphere System Using Human Neural Progenitor Cells
In this study, human neural progenitor cells cultured as a 3D neurosphere model were used to study the effects of PAMAM dendrimers on the nervous system. Neurospheres were exposed to different G4-PAMAM dendrimers for 72 h at concentrations of 0.3, 1, 3, and 10 μg/ml. The biodistribution was investigated using fluorescence-labeled PAMAM dendrimers, and gene expression was evaluated using microarray analysis followed by pathway and network analysis. Results showed that PAMAM dendrimer nanoparticles can penetrate into neurospheres via superficial cells on them. PAMAM-NH2 but not PAMAM-SC can inhibit neurosphere growth. A r...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Zeng, Y., Kurokawa, Y., Zeng, Q., Win-Shwe, T.-T., Nansai, H., Zhang, Z., Sone, H. Tags: Three-Dimensional Neurosphere System and Polyamidoamine Source Type: research
Sirtuin 3 Protects against Urban Particulate Matter-Induced Autophagy in Human Bronchial Epithelial Cells
In this study, we examined the role of SIRT3 in the regulation of urban PM-induced oxidative stress in normal primary human bronchial epithelial cells (HBEpiCs). Cell viability showed a time- and concentration-dependent decrease when exposed to urban PM, which could indicate that the amount of lactate dehydrogenase released from the cell in response to urban PM is related to cell viability in HBEpiC. The effects of urban PM on morphological and biochemical markers of autophagy in HBEpiC were analyzed by electron microscopy and Western blotting. Overexpression of SIRT3 inhibited urban PM-induced ROS generation, while concom...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Chen, I.- C., Huang, H.-H., Chen, P.-F., Chiang, H.-C. Tags: Protective Role of Sirtuin 3 from Particulate Matter in Bronchial Epithelium Source Type: research
Cardiac Non-myocyte Cells Show Enhanced Pharmacological Function Suggestive of Contractile Maturity in Stem Cell Derived Cardiomyocyte Microtissues
The immature phenotype of stem cell derived cardiomyocytes is a significant barrier to their use in translational medicine and pre-clinical in vitro drug toxicity and pharmacological analysis. Here we have assessed the contribution of non-myocyte cells on the contractile function of co-cultured human embryonic stem cell derived cardiomyocytes (hESC-CMs) in spheroid microtissue format. Microtissues were formed using a scaffold free 96-well cell suspension method from hESC-CM cultured alone (CM microtissues) or in combination with human primary cardiac microvascular endothelial cells and cardiac fibroblasts (CMEF microtissue...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Ravenscroft, S. M., Pointon, A., Williams, A. W., Cross, M. J., Sidaway, J. E. Tags: Function of Non-Myocyte Cells Derived from Stem Cell Cardiomyocyte Model Source Type: research
A Role for Regulatory T Cells in a Murine Model of Epicutaneous Toluene Diisocyanate Sensitization
Toluene diisocyanate (TDI) is a leading cause of chemical-induced occupational asthma which impacts workers in a variety of industries worldwide. Recently, the robust regulatory potential of regulatory T cells (Tregs) has become apparent, including their functional role in the regulation of allergic disease; however, their function in TDI-induced sensitization has not been explored. To elucidate the kinetics, phenotype, and function of Tregs during TDI sensitization, BALB/c mice were dermally exposed (on each ear) to a single application of TDI (0.5–4% v/v) or acetone vehicle and endpoints were evaluated via RT-PCR a...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Long, C. M., Marshall, N. B., Lukomska, E., Kashon, M. L., Meade, B. J., Shane, H., Anderson, S. E. Tags: Regulatory T Cells Mediate Toluene Diisocynatate Sensitization Source Type: research
Preclinical Safety Profile of a Depleting Antibody against CRTh2 for Asthma: Well Tolerated Despite Unexpected CRTh2 Expression on Vascular Pericytes in the Central Nervous System and Gastric Mucosa
CRTh2 is expressed on immune cells that drive asthma pathophysiology. Current treatment options for severe asthma are inadequate and therapeutic antibody-mediated depletion of CRTh2-expressing cells represents a promising new therapeutic strategy. Here we report for the first time that CRTh2 is not only expressed on immune cells, but also on microvasculature in the central nervous system (CNS) and gastric mucosa in humans. Microvascular expression of CRTh2 raises a safety concern because a therapeutic antiCRTh2 antibody with enhanced depletion capacity could lead to vascular damage. To evaluate this safety risk, we charact...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Rajapaksa, K. S., Huang, T., Sharma, N., Liu, S., Solon, M., Reyes, A., Paul, S., Yee, A., Tao, J., Chalasani, S., Bien-Ly, N., Barck, K., Carano, R. A. D., Wang, J., Rangell, L., Bremer, M., Danilenko, D. M., Katavolos, P., Hotzel, I., Reif, K., Austin, Tags: Safety Profile of Antibody-Based Treatment of Asthma Source Type: research
Arsenite and Cadmium Activate MAPK/ERK via Membrane Estrogen Receptors and G-Protein Coupled Estrogen Receptor Signaling in Human Lung Adenocarcinoma Cells
This study supports the involvement of membrane ER and GPER signaling in mediating cellular responses to environmentally relevant nM concentrations of CdCl2 and NaAsO2 in lung adenocarcinoma cells. (Source: Toxicological Sciences)
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Huff, M. O., Todd, S. L., Smith, A. L., Elpers, J. T., Smith, A. P., Murphy, R. D., Bleser-Shartzer, A. S., Hoerter, J. E., Radde, B. N., Klinge, C. M. Tags: MAPK/ERK Activation by Arsenite and Cadmium Source Type: research
Di(2-Ethylhexyl) Phthalate Exposure In Utero Damages Sertoli Cell Differentiation Via Disturbance of Sex Determination Pathway in Fetal and Postnatal Mice
Mice may share similar mechanism with human underlying reproductive toxicity induced by di(2-ethylhexyl) phthalate (DEHP), which is not supposed to be associated with decreased testicular testosterone. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure level. After in utero DEHP exposure, loss of Sertoli cells and germ cells were observed in the male pups at postnatal days 21. And SRY-related HMG box 9 (SOX9), Fibroblast growth factor-9 (FGF9), and Double-sex and Mab-3 related transcripttion factor 1 (DMRT1) proteins were significantly downregulated by DEHP at 2 mg/kg/...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Wang, Y., Yang, Q., Liu, W., Yu, M., Zhang, Z., Cui, X. Tags: Developmental Phthalate Exposure Disrupts Sertoli Cell Differentiation Source Type: research
Generation of a New Model Rat: Nrf2 Knockout Rats Are Sensitive to Aflatoxin B1 Toxicity
In this study, we generated 2 lines of Nrf2 knockout rats by using a genome editing technology; 1 line harbors a 7-bp deletion (7) and the other line harbors a 1-bp insertion (+1) in the Nrf2 gene. In the livers of rats homozygously deleting the Nrf2 gene, an activator of Nrf2 signaling, CDDO-Im, could not induce expression of representative Nrf2 target genes. To examine altered toxicological response, we treated the Nrf2 knockout rats with aflatoxin B1 (AFB1), a carcinogenic mycotoxin that elicits gene mutations through binding of its metabolites to DNA and for which the rat has been proposed as a reasonable surrogate for...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Taguchi, K., Takaku, M., Egner, P. A., Morita, M., Kaneko, T., Mashimo, T., Kensler, T. W., Yamamoto, M. Tags: Nrf2 Knockout Rats and Aflatoxin Toxicity Source Type: research
Arsenic Metabolism in Children Differs From That in Adults
Arsenic toxicity in adults is associated with methylation efficiency, influenced by factors such as gender, genetics, and nutrition. The aim of this study was to evaluate influencing factors for arsenic metabolism in children. For 488 children (9 years), whose mothers participated in a study on arsenic exposure during pregnancy (nested into the MINIMat trial) in rural Bangladesh, we measured urinary concentrations of inorganic arsenic (iAs) and its metabolites methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by HPLC-HG-ICPMS. Methylation efficiency was assessed by relative amounts (%) of the metabolites. We evaluate...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Skröder Löveborn, H., Kippler, M., Lu, Y., Ahmed, S., Kuehnelt, D., Raqib, R., Vahter, M. Tags: Altered Arsenic Metabolism in Children Source Type: research
Ozone Inhalation Provokes Glucocorticoid-Dependent and -Independent Effects on Inflammatory and Metabolic Pathways
Growing evidence implicates air pollutants in adverse health effects beyond respiratory and cardiovascular disease, including metabolic impacts (diabetes, metabolic syndrome, obesity) and neurological/neurobehavioral outcomes (neurodegenerative disease, cognitive decline, perceived stress, depression, suicide). We have shown that inhalation of particulate matter or ozone activates the hypothalamic–pituitary–adrenal axis in rats and increases plasma levels of the glucocorticoid corticosterone. To investigate the role of corticosterone in mediating inflammatory and metabolic effects of pollutant exposure, in this...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Thomson, E. M., Pal, S., Guenette, J., Wade, M. G., Atlas, E., Holloway, A. C., Williams, A., Vincent, R. Tags: Ozone-Induced Effects on Glucocorticoid Signaling Source Type: research
The Emergence of Systematic Review in Toxicology
The Evidence-based Toxicology Collaboration hosted a workshop on "The Emergence of Systematic Review and Related Evidence-based Approaches in Toxicology," on November 21, 2014 in Baltimore, Maryland. The workshop featured speakers from agencies and organizations applying systematic review approaches to questions in toxicology, speakers with experience in conducting systematic reviews in medicine and healthcare, and stakeholders in industry, government, academia, and non-governmental organizations. Based on the workshop presentations and discussion, here we address the state of systematic review methods in toxicology, histo...
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Authors: Stephens, M. L., Betts, K., Beck, N. B., Cogliano, V., Dickersin, K., Fitzpatrick, S., Freeman, J., Gray, G., Hartung, T., McPartland, J., Rooney, A. A., Scherer, R. W., Verloo, D., Hoffmann, S. Tags: Forum: Systematic Reviews in Toxicology Source Type: research
Table of Contents
(Source: Toxicological Sciences)
Source: Toxicological Sciences - June 26, 2016 Category: Toxicology Tags: Standing Material Source Type: research
