Journal of Applied Toxicology

Cover image for Vol. 31 Issue 5

July 2011

Volume 31, Issue 5

Pages 379–498

  1. Reviews

    1. Top of page
    2. Reviews
    3. Research Articles
    4. Short Communications
    1. A review of studies on androgen and estrogen exposure in fish early life stages: effects on gene and hormonal control of sexual differentiation (pages 379–398)

      Jessica K. Leet, Heather E. Gall and Maria S. Sepúlveda

      Article first published online: 10 MAY 2011 | DOI: 10.1002/jat.1682

      Even at low concentrations hormones in the environment are of concern for teleost fishes, especially at early life stages. This review is a brief overview of the sources of steroid hormones in the environment, sex differentiation in fish and publications on early life stage fish exposed to various hormones found in the environment. The publications reviewed mainly focus on modes of action and effects of androgens and estrogens on sex differentiation and gonadal development in various model fish species.

  2. Research Articles

    1. Top of page
    2. Reviews
    3. Research Articles
    4. Short Communications
    1. Use of GC × GC/TOF-MS and LC/TOF-MS for metabolomic analysis of Hyalella azteca chronically exposed to atrazine and its primary metabolite, desethylatrazine (pages 399–410)

      Kimberly J. Ralston-Hooper, Jiri Adamec, Amber Jannash, Robert Mollenhauer, Hugo Ochoa-Acuña and Maria S. Sepúlveda

      Article first published online: 18 SEP 2010 | DOI: 10.1002/jat.1587

      Atrazine is a commonly detected water contaminant. Little information is available on atrazine's metabolite desethylatrazine (DEA). We used metabolomics to examine metabolite profiles of Hyalella azteca exposed to 30 µg/L atrazine and DEA. The majority of metabolites were lipids and by-products of β-oxidation of fatty acids suggesting possible disruption in energy metabolism. Eicosanoids increased in exposed females suggesting perturbations in neuropeptide hormonal systems. This research demonstrates the feasibility of utilizing both GC × GC and LC TOF-MS for metabolomic profiling of invertebrates.

    2. Biocompatible gellan gum-reduced gold nanoparticles: cellular uptake and subacute oral toxicity studies (pages 411–420)

      Sheetal Dhar, Vishal Mali, Subhash Bodhankar, Anjali Shiras, B. L. V. Prasad and Varsha Pokharkar

      Article first published online: 19 NOV 2010 | DOI: 10.1002/jat.1595

      The study pertains to the cellular uptake and toxicity of gold nanoparticles synthesized using a microbial polysaccharide, gellan gum, as a capping and reducing agent. The current findings, while establishing the specific uptake of nanoparticles into cancerous cells, also demonstrates that the gellan gum-reduced gold nanoparticles were devoid of toxicity in animals following oral administration.

    3. Finding maximal transcriptome differences between reprotoxic and non-reprotoxic phthalate responses in rat testis (pages 421–430)

      Xiaolian Yuan, Martijs J. Jonker, Jillian de Wilde, Aart Verhoef, Floyd R.A. Wittink, Jan van Benthem, Jos G. Bessems, Betty C. Hakkert, Raoul V. Kuiper, Harry van Steeg, Timo M. Breit and Mirjam Luijten

      Article first published online: 9 NOV 2010 | DOI: 10.1002/jat.1601

      In vivo toxicity testing can potentially be improved by the introduction of microarray technology. We investigated the potential of applying toxicogenomics in reprotoxicity testing in an exposure study with reprotoxic and non-reprotoxic phthalates. Tissue from testis from treated male rats was used for concurrent histopathological and transcriptome analyses. We identified the maximal transcriptome differences between reprotoxic and non-reprotoxic phthalate responses in our study and showed that a transcriptomics approach may lead to predictive biomarkers for reprotoxic phthalates.

    4. Long-term feeding effects of stevioside sweetener on some toxicological parameters of growing male rats (pages 431–438)

      Hala A. Awney, Mona I. Massoud and Samia El-Maghrabi

      Article first published online: 19 NOV 2010 | DOI: 10.1002/jat.1604

      The effects of stevioside low dose (SL), high dose (SH) and low dose with inulin (SL + I) on young male rats for 12 weeks was investigated. Although the SL dose was higher than the stevioside temporary accepted daily intake, no toxicological effects were observed in SL or SL + I. Treatment with SH caused significant changes in all investigated toxicological parameters which considered as a toxic dose.

    5. Nano-CuO inhibited voltage-gated sodium current of hippocampal CA1 neurons via reactive oxygen species but independent from G-proteins pathway (pages 439–445)

      Zhaowei Liu, Shichang Liu, Guogang Ren, Tao Zhang and Zhuo Yang

      Article first published online: 7 JAN 2011 | DOI: 10.1002/jat.1611

      The aim of this study was to investigate the effects of nano-CuO on voltage-gated sodium current (INa) in hippocampal CA1 neurons. The results suggested that nano-CuO inhibited amplitudes of INa currents and prolonged peak rise time of action potential (AP). The responses to nano-CuO were inhibited by reactive oxygen species (ROS) scavenger. However, the G-proteins inhibitor did not block the effects of nano-CuO. The effects of nano-CuO were mediated through activation of ROS-INa-AP signaling cascades and independent from G-proteins pathway.

    6. A novel method for measuring aromatase activity in tissue samples by determining estradiol concentrations (pages 446–454)

      H. Tinwell, J. B. Rascle, S. Colombel, I. Al Khansa, A. Freyberger and R. Bars

      Article first published online: 24 JAN 2011 | DOI: 10.1002/jat.1623

      Effects on aromatase are considered an integral part of the evaluation of chemicals for endocrine disruption as this enzyme is responsible for the homeostatic balance between androgens and estrogens. A simple but highly specific assay has been developed that measures the estradiol end-product of the aromatase reaction rather than the tritiated water by-product. The assay has been successfully applied to tissue samples. Our data have shown that both enzyme inhibition and induction can be unequivocally identified with this method.

    7. Pathway analysis of gene expression in local lymph nodes draining skin exposed to three different sensitizers (pages 455–462)

      Hyun-Ok Ku, Sang-Hee Jeong, Hwan-Goo Kang, Seong-Wan Son, So-mi Yun and Doug-Young Ryu

      Article first published online: 15 MAR 2011 | DOI: 10.1002/jat.1646

      Genomic analysis in the local lymph node assays (LLNAs) is useful for assessing skin sensitization of chemicals and providing insights into mechanisms of sensitization. In this study, we collected 1406 genes from previous microarray findings, validated changes in their expression by RT-PCR analysis in local lymph nodes draining skin exposed to different sensitizers, and interpreted their biological function through pathway-based genomic analysis, in which 468 genes were identified as being in the KEGG pathway database. The top-ranked functions (P < 0.01) identified as being affected by the sensitizers were associated with aspects of cell growth, such as DNA replication, cell cycle regulation and pyrimidine metabolism. All the sensitizers tested (DNCB, OXA and TDI) induced significant up-regulation of Psme4, Tfdp1 and Dut identified in these functional categories. Specific changes were also shown in functional categories related to the immune response, such as Ccl21c, Cxcl9, Cxcl10, Ifng and Il12rb1, which were found to have functional relevance. These findings may enhance our understanding and assessment of chemical sensitizers, and enable us to distinguish sensitizers from irritants and to classify chemicals as contact sensitizers.

    8. Proteomic analysis of the differentially expressed proteins by airborne nanoparticles (pages 463–470)

      Seul Ki Park, Yu Mi Jeon, Bu Soon Son, Hyung Sun Youn and Mi Young Lee

      Article first published online: 14 APR 2011 | DOI: 10.1002/jat.1658

      Airborne nanoparticles with thermodynamic diameters less than 56 nm (PM0.056) were collected using a MOUDI cascade impactor, and the differentially expressed proteins upon exposure to PM0.056 were identified in human bronchial epithelial cells. More than 600 protein spots were detected on the two-dimensional gel, and the identified 13 of these proteins showed notable changes. Nine were up-regulated and four were down-regulated following treatment with the airborne nanoparticles.

    9. Nervous system effects of dissolved and nanoparticulate cadmium in rats in subacute exposure (pages 471–476)

      Edina Horváth, Gábor Oszlánczi, Zsuzsanna Máté, Andrea Szabó, Gábor Kozma, András Sápi, Zoltán Kónya, Edit Paulik, László Nagymajtényi and András Papp

      Article first published online: 23 FEB 2011 | DOI: 10.1002/jat.1664

      To model human cadmium exposure, rats were subacutely treated with CdCl2 solution per os (3.0 mg kg−1 b.w.) or nanoparticulate CdO2 (particle size ca 65 nm) by intratracheal instillation (0.04 mg kg−1 b.w.) alone and in sequential combination. Three weeks of oral plus one week of intratracheal exposure caused significant reduction of body weight gain and open field motility. Latency of sensory evoked potentials increased in all treated rats. Some effects suggested potentiating interaction between the two forms of Cd.

    10. Delayed response in the rat frontal lobe transcriptome to perinatal exposure to the flame retardant BDE-47 (pages 477–483)

      Alexander Suvorov and Larissa Takser

      Article first published online: 11 MAR 2011 | DOI: 10.1002/jat.1667

      BDE-47 is the brominated flame retardant prevalent in human tissues and nature and known to have endocrine and behavioral disrupting properties in animals. We exposed pregnant Wistar rats to low doses of BDE-47 perinatally and analyzed gene expression profile in brain frontal lobe on PND41. Clusters of genes involved in nerve impulse transmission, nervous system development and functioning, and core biosynthetic processes were altered, including several downregulated genes of cation channels. Representation of LINE1 RNA was decreased significantly.

    11. Changes in the levels of DNA methylation in testis and liver of SD rats neonatally exposed to 5-aza-2′-deoxycytidine and cadmium (pages 484–495)

      Hongyan Zhu, Keyong Li, Jiren Liang, Jie Zhang and Qing Wu

      Article first published online: 30 MAR 2011 | DOI: 10.1002/jat.1673

      To investigate the changes in the levels of DNA methylation in the testis during development after neonatal transient exposure to DNA methyltransferase (DNMT) inhibitors, we orally administered Sprague -Dawley (SD) rats with 5-aza-2′-deoxycytidine or cadmium daily from days 3 to 7 postpartum. Sperm numbers, DNMT activity, as well as DNA methylation level in LINE-1, in the p53 gene promoter region and in the c-fos coding region were showed in day 8 and day 70 in the present study.

  3. Short Communications

    1. Top of page
    2. Reviews
    3. Research Articles
    4. Short Communications
    1. Increased expression of miR-34a in mouse spleen one day after exposure to N-ethyl-N-nitrosourea (pages 496–498)

      David Chen, Zhiguang Li and Tao Chen

      Article first published online: 25 JAN 2011 | DOI: 10.1002/jat.1640

      miR-34a plays an important role in controlling cell proliferation and apoptosis. Its expression is often down-regulated in human cancers and up-regulated in tissues exposed to genotoxins. In this report, the expression change of miR-34a induced by acute treatment of the mutagen ENU in mouse spleen was examined. miR-34a expression was up-regulated by 5.5 fold over the controls one day after the treatment, indicating that miR-34a has the potential to be a early biomarker for genotoxin exposure.

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