Journal of Applied Toxicology

Cover image for Journal of Applied Toxicology

April 2010

Volume 30, Issue 3

Pages 183–289

  1. Reviews

    1. Top of page
    2. Reviews
    3. Research Articles
    4. Short Communications
    5. Letter to the Editor
    1. You have free access to this content
      Genotoxicity of pyrrolizidine alkaloids (pages 183–196)

      Tao Chen, Nan Mei and Peter P. Fu

      Article first published online: 28 JAN 2010 | DOI: 10.1002/jat.1504

      Pyrrolizidine alkaloids (PAs) from many plants are toxic to livestock, wildlife and human. Many of them are genotoxic and tumorigenic. Upon metabolic activation, PAs produce DNA adducts, DNA cross-linking, DNA breaks, sister chromatid exchange, micronuclei, chromosomal aberrations, gene mutations, and chromosome mutations invivo and in vitro. The signature types of mutations are G : C [RIGHTWARDS ARROW] T : A transversion and tandem base substitutions. Overall, PAs are mutagenic and their mutagenicity appears to be responsible for the carcinogenesis of PAs.

  2. Research Articles

    1. Top of page
    2. Reviews
    3. Research Articles
    4. Short Communications
    5. Letter to the Editor
    1. Physiological condition status and muscle-based biomarkers in rainbow trout (Oncorhynchus mykiss), after long-term exposure to carbamazepine (pages 197–203)

      Zhi-Hua Li, Vladimir Zlabek, Josef Velisek, Roman Grabic, Jana Machova and Tomas Randak

      Article first published online: 15 SEP 2009 | DOI: 10.1002/jat.1482

      Recently, residual pharmaceuticals are generally recognized as relevant sources of aquatic environmental pollutants. However, the toxicological effects of these contaminants have not been adequately researched. In this study, the chronic toxic effects of carbamazepine (CBZ) on physiological condition status and muscle-based biomarkers of rainbow trout were investigated, including morphological indices and energy metabolic parameters, as well as antioxidant enzymes activities and oxidative stress markers.

    2. Ifosfamide metabolite chloroacetaldehyde inhibits cell proliferation and glucose metabolism without decreasing cellular ATP content in human breast cancer cells MCF-7 (pages 204–211)

      Burhan Knouzy, Laurence Dubourg, Gabriel Baverel and Christian Michoudet

      Article first published online: 22 SEP 2009 | DOI: 10.1002/jat.1485

      Chloroacetaldehyde, the main product of ifosfamide metabolism inhibits breast cancer cell proliferation. This inhibition is linked to the decrease of glucose utilization, mainly explained by the decrease of glucose transport and hexokinase activity. This inhibition is not related to a drop of ATP cellular content but rather due to a reduction of biosynthetic precursors from glycolytic intermediates. Our results suggest that chloroacetaldehyde could contribute to ifosfamide therapeutic efficacy against cancer cells.

    3. You have free access to this content
      Cellular uptake and toxicity of gold nanoparticles in prostate cancer cells: a comparative study of rods and spheres (pages 212–217)

      Arnida, Alexander Malugin and Hamidreza Ghandehari

      Article first published online: 9 NOV 2009 | DOI: 10.1002/jat.1486

      Using a series of gold nanoparticles with incremental increase in dimensions but varying geometries (spherical vs rods) we have evaluated the influence of shape, size, surface properties and concentration on cellular uptake, adsorption of proteins and toxicity in a human prostate cancer cell line (PC-3). In the range of 30–90 nm diameter studied, spherical particles of 50 nm in diameter without poly(ethylene glycol) (PEG) had the highest uptake. Surface attachment of PEG reduced cellular uptake of gold nanoparticles.

    4. Direct-oxidative DNA damage and apoptosis induction in different human respiratory cells exposed to low concentrations of sodium chromate (pages 218–225)

      Delia Cavallo, Cinzia Lucia Ursini, Anna Maria Fresegna, Aureliano Ciervo, Raffaele Maiello, Bruna Rondinone, Velia D'Agata and Sergio Iavicoli

      Article first published online: 16 OCT 2009 | DOI: 10.1002/jat.1487

      In this study cytotoxic, genotoxic and oxidative effects induced on human lung alveolar (A549) and bronchial (BEAS-2B) cells by short (0.5–4 h) exposure to low doses (1–10 µM) of sodium chromate were evaluated. Cytotoxicity was evaluated by MTT test, apoptotic morphological analysis and caspase-3 activity. Genotoxicity and oxidative DNA damage were evaluated by Fpg comet assay. The results did not show significant cytotoxic effects, while genotoxic effects, particularly in A549 cells, and a transient oxidative DNA damage in both cell lines were found.

    5. Thinner inhalation effects on oxidative stress and DNA repair in a rat model of abuse (pages 226–232)

      Minerva Martínez-Alfaro, Alfonso Cárabez-Trejo, Marco-Antonio Gallegos-Corona, Gustavo Pedraza-Aboytes, Nancy Georgina Hernández-Chan and Guillermo Enrique Leo-Amador

      Article first published online: 2 NOV 2009 | DOI: 10.1002/jat.1488

      Genotoxic effects of thinner inhalation in an animal model of thinner abuse were examined. Thinner inhalation in our experimental condition is able to induce weight loss, lung abnormalities, and oxidative stress. This oxidative stress induces oxidative DNA damage that is not a characteristic feature of genotoxic damage. No significant difference in DNA damage and DNA repair (biomarkers of genotoxicity) in lymphocytes from thinner-treated and control rats was found. Absence of hemopoietic and genotoxicity could be explained by the absence of benzene.

    6. Post-partum testosterone administration does not reverse the effects of perinatal exposure to cadmium on rat offspring development (pages 233–241)

      R. Couto-Moraes, L. F. Felicio and M. M. Bernardi

      Article first published online: 21 OCT 2009 | DOI: 10.1002/jat.1489

      Perinatal high cadmium dose exposure from gestational days 18 to 21, and until the 7th lactation day, induced maternal toxicity and a delay in offspring physical and reflexes development. The immediate postpartum testosterone administration, except in body length gain, was not able to reverse toxic cadmium effects. These results indicate that perinatal cadmium promoted changes in the development of male rat offspring, reprogramming the pup's development and that testosterone administration was not able to reverse the cadmium effects.

    7. Metals in human placenta: focus on the effects of cadmium on steroid hormones and leptin (pages 242–253)

      Sandra Stasenko, Elease M. Bradford, Martina Piasek, Michael C. Henson, Veda M. Varnai, Jasna Jurasović and Vesna Kušec

      Article first published online: 21 OCT 2009 | DOI: 10.1002/jat.1490

      Cadmium is an acknowledged endocrine disrupting chemical and a metalloestrogen. Concentrations of cadmium, lead, essential elements and steroid hormones were assessed in placental tissue of healthy parturients (109 non-smokers and 99 smokers). Placental cadmium concentrations in smokers were twice that of non-smokers, and lead and zinc were significantly increased. Placental concentrations of iron, copper, progesterone and estradiol were unchanged. Leptin mRNA was quantified in human trophoblast cells co-cultured with CdCl2. Cadmium exposure caused a decrease in leptin mRNA transcript abundance.

    8. Protective effect of rosmarinic acid on V79 cells evaluated by the micronucleus and comet assays (pages 254–259)

      Ricardo Andrade Furtado, Felipe Rodrigues Rezende de Araújo, Flávia Aparecida Resende, Wilson Roberto Cunha and Denise Crispim Tavares

      Article first published online: 21 OCT 2009 | DOI: 10.1002/jat.1491

      The aim of this study was to investigate the ability of RA to prevent chemically induced chromosome breakage or loss and primary DNA damage using the micronucleus and comet assays with V79 cells, respectively. The results showed that RA exerted no genotoxic effect, but significantly reduced the frequency of micronuclei and the extent of DNA damage induced by DXR at the three concentrations tested. The antioxidant activity of RA might be involved in the reduction of DXR-induced DNA damage.

    9. Genetic association between intronic variants in AS3MT and arsenic methylation efficiency is focused on a large linkage disequilibrium cluster in chromosome 10 (pages 260–270)

      Paulina Gomez-Rubio, Maria M. Meza-Montenegro, Ernesto Cantu-Soto and Walter T. Klimecki

      Article first published online: 14 DEC 2009 | DOI: 10.1002/jat.1492

      Several AS3MT single nucleotide polymorphisms (SNPs) that previously were associated with arsenic methylation efficiency have also shown strong linkage-disequilibrium (LD) in the genomic region including AS3MT. To characterize the extent of LD in this region, 46 SNPs were genotyped in chromosome 10. Strong LD was observed spanning a region that includes AS3MT and four other genes. Genetic association analysis confirmed the association between this large cluster of linked polymorphisms and arsenic methylation efficiency.

    10. Cytochrome P450-dependent toxicity of dapsone in human erythrocytes (pages 271–275)

      Shobana Ganesan, Rajnish Sahu, Larry A Walker and Babu L. Tekwani

      Article first published online: 8 DEC 2009 | DOI: 10.1002/jat.1493

      Dapsone metabolites generated through cytochrome P450 (CYP) mediated reactions are responsible for its hemolytic side effects. An in vitro metabolism-linked assay was employed to profile CYP isoforms responsible for hemotoxicity of dapsone. The metabolism through CYP 2C19 contributed maximally to its hemotoxic effects with minor contributions from CYP2B6, CYP2D6 and CYP3A4. Abrogation of hemotoxic effects of dapsone by cimetidine and chloramphenicol further confirmed predominant contribution of CYP2C19 mediated metabolism.

    11. Interactions of aluminum nanoparticles with human epidermal keratinocytes (pages 276–285)

      Nancy A. Monteiro-Riviere, Steven J. Oldenburg and Alfred O. Inman

      Article first published online: 9 DEC 2009 | DOI: 10.1002/jat.1494

      Aluminum nanoparticles (Al NP) are used in applications as diverse as drug delivery, material surface coatings and an ingredient for solid rocket fuel. To understand interactions and biological activity of Al NP in human cells, cultured neonatal epidermal keratinocytes (HEK) were exposed 24 h to 50 and 80 nm NP. HEK viability did not decrease following NP exposure. UV-Vis and NP controls revealed that Al interacts with assay dyes. Our studies illustrate the difficulties involved in assessing the safety of nanomaterials.

  3. Short Communications

    1. Top of page
    2. Reviews
    3. Research Articles
    4. Short Communications
    5. Letter to the Editor
    1. Updating the Skin Sensitization in Vitro Data Assessment Paradigm in 2009 – a chemistry and QSAR perspective (pages 286–288)

      David W. Roberts and Grace Y. Patlewicz

      Article first published online: 4 FEB 2010 | DOI: 10.1002/jat.1508

      This communication is stimulated by a recent Toxicology Update by Basketter and Kimber (2009), updating an earlier paradigm (Jowsey et al., 2006) for non-animal-based hazard identification of skin sensitizers. Basketter and Kimber discuss what they describe as key elements in the immunobiological sequence of steps involved in skin sensitization and propose a holistic approach of integrating information from several in vitro assays representing these key elements of the immunobiological mechanism of skin sensitization.

  4. Letter to the Editor

    1. Top of page
    2. Reviews
    3. Research Articles
    4. Short Communications
    5. Letter to the Editor
    1. Letter to the Editor (page 289)

      David Basketter and Ian Kimber

      Article first published online: 4 FEB 2010 | DOI: 10.1002/jat.1510