Editorial Board
(Source: Toxicological Sciences)
Source: Toxicological Sciences - August 30, 2016 Category: Toxicology Tags: Standing Material Source Type: research
The Literature of Science
(Source: Toxicological Sciences)
Source: Toxicological Sciences - August 30, 2016 Category: Toxicology Authors: Miller, G. W. Tags: Editorial Source Type: research
Cover
(Source: Toxicological Sciences)
Source: Toxicological Sciences - August 30, 2016 Category: Toxicology Tags: Cover Source Type: research
From the Editors Desk, Editors Highlights
(Source: Toxicological Sciences)
Source: Toxicological Sciences - August 30, 2016 Category: Toxicology Tags: Look Inside ToxSci Source Type: research
Pyrazinamide Induced Rat Cholestatic Liver Injury through Inhibition of FXR Regulatory Effect on Bile Acid Synthesis and Transport
Pyrazinamide (PZA) is an indispensable first-line drug used for the treatment of tuberculosis which may cause serious hepatotoxicity; however, the mechanisms underlying these toxicities are poorly understood. Cholestasis plays an important role in drug-induced liver injury. Since there were no previous published works reported cholestasis and PZA hepatotoxicity relationship, this study aimed to identify whether PZA can induce liver injury with characterized evidences of cholestasis and to clarify expression changes of proteins related to both bile acid synthesis and transport in PZA-induced liver injury. PZA (2 g/kg) was a...
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Guo, H.-L., Hassan, H. M., Zhang, Y., Dong, S.-Z., Ding, P.-P., Wang, T., Sun, L.-X., Zhang, L.-Y., Jiang, Z.-Z. Tags: FXR Regulation and Pyrazinamide Source Type: research
From the Cover: Disease-Induced Disparities in Formation of the Nanoparticle-Biocorona and the Toxicological Consequences
Nanoparticle (NP) association with macromolecules in a physiological environment forms a biocorona (BC), which alters NP distribution, activity, and toxicity. While BC formation is dependent on NP physicochemical properties, little information exists on the influence of the physiological environment. Obese individuals and those with cardiovascular disease exist with altered serum chemistry, which is expected to influence BC formation and NP toxicity. We hypothesize that a BC formed on NPs following incubation in hyperlipidemic serum will result in altered NP–BC protein content, cellular association, and toxicity comp...
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Shannahan, J. H., Fritz, K. S., Raghavendra, A. J., Podila, R., Persaud, I., Brown, J. M. Tags: Evaluation of the Nanoparticle Biocorona Source Type: research
Mechanisms of Doxorubicin Toxicity in Pancreatic {beta}-Cells
Exposure to chemotherapeutic agents has been linked to an increased risk of type 2 diabetes (T2D), a disease characterized by both the peripheral insulin resistance and impaired glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. Using the rat β-cell line INS-1 832/13 and isolated mouse pancreatic islets, we investigated the effect of the chemotherapeutic drug doxorubicin (Adriamycin) on pancreatic β-cell survival and function. Exposure of INS-1 832/13 cells to doxorubicin caused impairment of GSIS, cellular viability, an increase in cellular toxicity, as soon as 6 h post-exposure. Doxorubic...
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Heart, E. A., Karandrea, S., Liang, X., Balke, M. E., Beringer, P. A., Bobczynski, E. M., Zayas-Bazan Burgos, D., Richardson, T., Gray, J. P. Tags: Doxorubicin and Adverse Effects in Pancreatic [beta ]-Cells Source Type: research
Editor's Highlight: Identification and Characterization of Teratogenic Chemicals Using Embryonic Stem Cells Isolated From a Wnt/{beta}-Catenin-Reporter Transgenic Mouse Line
Embryonic stem cells (ESCs) are commonly used for the analysis of gene function in embryonic development and provide valuable models for human diseases. In recent years, ESCs have also become an attractive tool for toxicological testing, in particular for the identification of teratogenic compounds. We have recently described a Bmp-reporter ESC line as a new tool to identify teratogenic compounds and to characterize the molecular mechanisms mediating embryonic toxicity. Here we describe the use of a Wnt/β-Catenin-reporter ESC line isolated from a previously described mouse line that carries the LacZ reporter gene unde...
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Kugler, J., Kemler, R., Luch, A., Oelgeschläger, M. Tags: WNT/[beta ]-Catenin Signaling in ES Cells to Identify Teratogens Source Type: research
The Mouse Fetal Ovary Has Greater Sensitivity Than the Fetal Testis to Benzo[a]pyrene-Induced Germ Cell Death
This study provides a novel insight into molecular mechanisms by which BaP has direct gonadotoxicity in the mouse fetal ovary. (Source: Toxicological Sciences)
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Lim, J., Kong, W., Lu, M., Luderer, U. Tags: Increased Vulnerability of Mouse Fetal Ovary to Benzo(a)pyrene Source Type: research
Benzo(a)pyrene Is Mutagenic in Mouse Spermatogonial Stem Cells and Dividing Spermatogonia
Although many environmental agents are established male germ cell mutagens, few are known to induce mutations in spermatogonial stem cells. Stem cell mutations are of great concern because they result in a permanent increase in the number of mutations carried in sperm. We investigated mutation induction during mouse spermatogenesis following exposure to benzo(a)pyrene (BaP). MutaMouse males were given 0, 12.5, 25, 50, or 100 mg/kg bw/day BaP for 28 days by oral gavage. Germ cells were collected from the cauda epididymis and seminiferous tubules 3 days after exposure and from cauda epididymis 42 and 70 days after exposure. ...
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: OBrien, J. M., Beal, M. A., Yauk, C. L., Marchetti, F. Tags: Mutagenic Effects of Benzo(a)pyrene in Mouse Sperm Stem Cells Source Type: research
From the Cover: Arsenite Uncouples Mitochondrial Respiration and Induces a Warburg-like Effect in Caenorhabditis elegans
Millions of people worldwide are chronically exposed to arsenic through contaminated drinking water. Despite decades of research studying the carcinogenic potential of arsenic, the mechanisms by which arsenic causes cancer and other diseases remain poorly understood. Mitochondria appear to be an important target of arsenic toxicity. The trivalent arsenical, arsenite, can induce mitochondrial reactive oxygen species production, inhibit enzymes involved in energy metabolism, and induce aerobic glycolysis in vitro, suggesting that metabolic dysfunction may be important in arsenic-induced disease. Here, using the model organis...
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Luz, A. L., Godebo, T. R., Bhatt, D. P., Ilkayeva, O. R., Maurer, L. L., Hirschey, M. D., Meyer, J. N. Tags: Arsenite and Mitochondrial Function in C. Elegans Source Type: research
From the Cover: Structural Determinants of the Position of 2,3',4,4',5-Pentachlorobiphenyl (CB118) Hydroxylation by Mammalian Cytochrome P450 Monooxygenases
This study will contribute to understanding of the metabolic fates and toxicity of CB118 in vivo. (Source: Toxicological Sciences)
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Mise, S., Haga, Y., Itoh, T., Kato, A., Fukuda, I., Goto, E., Yamamoto, K., Yabu, M., Matsumura, C., Nakano, T., Sakaki, T., Inui, H. Tags: Structural Modeling of Pentachlorobiphenyl 118 Hydroxylation Source Type: research
Editor's Highlight: Analysis of the Effects of Cell Stress and Cytotoxicity on In Vitro Assay Activity Across a Diverse Chemical and Assay Space
Chemical toxicity can arise from disruption of specific biomolecular functions or through more generalized cell stress and cytotoxicity-mediated processes. Here, responses of 1060 chemicals including pharmaceuticals, natural products, pesticidals, consumer, and industrial chemicals across a battery of 815 in vitro assay endpoints from 7 high-throughput assay technology platforms were analyzed in order to distinguish between these types of activities. Both cell-based and cell-free assays showed a rapid increase in the frequency of responses at concentrations where cell stress/cytotoxicity responses were observed in cell-bas...
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Judson, R., Houck, K., Martin, M., Richard, A. M., Knudsen, T. B., Shah, I., Little, S., Wambaugh, J., Woodrow Setzer, R., Kothya, P., Phuong, J., Filer, D., Smith, D., Reif, D., Rotroff, D., Kleinstreuer, N., Sipes, N., Xia, M., Huang, R., Crofton, K., T Tags: Computational Analysis of In Vitro Toxicology for Cell Stress and Cytotoxicity Source Type: research
3,3',4,4',5-Pentachlorobiphenyl (PCB 126) Decreases Hepatic and Systemic Ratios of Epoxide to Diol Metabolites of Unsaturated Fatty Acids in Male Rats
Disruption of the homeostasis of oxygenated regulatory lipid mediators (oxylipins), potential markers of exposure to aryl hydrocarbon receptor (AhR) agonists, such as 3,3',4,4',5-pentachlorobiphenyl (PCB 126), is associated with a range of diseases, including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Here we test the hypothesis that PCB 126 exposure alters the levels of oxylipins in rats. Male Sprague-Dawley rats (5-weeks old) were treated over a 3-month period every 2 weeks with intraperitoneal injections of PCB 126 in corn oil (cumulative doses of 0, 19.8, 97.8, and 390 µg/kg b.w.; 6 inject...
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: Wu, X., Yang, J., Morisseau, C., Robertson, L. W., Hammock, B., Lehmler, H.-J. Tags: PCB 126 Alters Unsaturated Fatty Acid Homeostasis Source Type: research
Editor's Highlight: Hydroxyurea Exposure Activates the P53 Signaling Pathway in Murine Organogenesis-Stage Embryos
Hydroxyurea, an anticancer agent and potent teratogen, induces oxidative stress and activates a DNA damage response pathway in the gestation day (GD) 9 mouse embryo. To delineate the stress response pathways activated by this drug, we investigated the effect of hydroxyurea exposure on the transcriptome of GD 9 embryos. Timed pregnant CD-1 mice were treated with saline or hydroxyurea (400 mg/kg or 600 mg/kg) on GD 9; embryonic gene and protein expression were examined 3 h later. Microarray analysis revealed that the expression of 1346 probe sets changed significantly in embryos exposed to hydroxyurea compared with controls;...
Source: Toxicological Sciences - July 24, 2016 Category: Toxicology Authors: El Husseini, N., Schlisser, A. E., Hales, B. F. Tags: P53 Signaling and Organogenesis Source Type: research
