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Dolan L.C.,Burdock Group | Hofman-Huther H.,BSL BIOSERVICE Scientific Laboratories GmbH | Amann N.,Wacker Chemie AG
BMC Research Notes | Year: 2014

Background: Hydroxytyrosol is naturally found in olives, olive oil and wine, and is consumed as part of a normal diet.The substance may have utility as a preservative in a wide variety of foods due to its antioxidant, antimicrobial and amphipathic properties.The potential for hydroxytyrosol to cause chromosome aberrations in vitro had been tested previously, with positive results at high concentrations. An OECD Guideline 475 study (mammalian bone marrow chromosome aberration test) was conducted in rats with the oral limit dose of 2000 mg/kg bw to determine whether hydroxytyrosol is a clastogen in vivo. Results: The oral limit dose of 2000 mg/kg hydroxytyrosol was well tolerated by most rats; however, some rats exhibited clinical signs that abated within 24 hours. Treatment with hydroxytyrosol did not significantly enhance the number of aberrant cells or the mitotic index 24 or 48 hours post-dose.The positive control (cyclophosphamide) induced the expected increase in chromosomal aberrations and a decrease in the mitotic index, confirming the validity of the assay. Conclusion: An oral limit dose of 2000 mg/kg hydroxytyrosol does not induce chromosome aberrations in bone marrow cells of the rat. Accordingly, hydroxytyrosol is not a clastogen in vivo. © 2014 Dolan et al.

Zanucco E.,Max Planck Institute of Biochemistry | El-Nikhely N.,Max Planck Institute for Heart and Lung Research | Gotz R.,University of Wurzburg | Gotz R.,Institute for Clinical Neurobiology | And 8 more authors.
Journal of Biological Chemistry | Year: 2014

Background: The regulation of RAF kinases is a highly complex process.Results: Loss of B-RAF in alveolar epithelial type II cells does not inhibit oncogenic C-RAF BxB-driven lung tumor initiation but diminishes MAPK signaling and tumor growth.Conclusion: B-RAF cooperates with oncogenic C-RAF BxB in lung tumorigenesis.Significance: Inhibition of RAFs dimerization might be a new therapeutic option for oncogenic C-RAF-driven tumors. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Lynch B.,Intertek | Lau A.,Intertek | Baldwin N.,Intertek | Hofman-Huther H.,BSL BIOSERVICE Scientific Laboratories GmbH | And 2 more authors.
Food and Chemical Toxicology | Year: 2013

Hoodia parviflora is being developed commercially for use in weight loss food and dietary supplement products. Its effects are ascribed to a number of glycosides that have been shown to be present in plant extracts from several Hoodia species, the best known of which is H. gordonii. H. parviflora has been identified as an alternative to H. gordonii, and, as part of the process to develop H. parviflora, in vitro genotoxicity tests, as recommended by recent European Food Safety Authority guidance, were conducted on a dried powder preparation of H. parviflora aerial parts. The preparation was tested for reverse mutation at doses up to 5,000 μg/plate in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, and in Escherichia coli WP2 uvrA TA, both in the presence and in the absence of an exogenous source of metabolic activation (rat liver S9). In addition, the dried powder was evaluated in an in vitro cytotoxicity chromosome aberration assay using human lymphocytes. Test conditions included both a 4 (up to 2500 μg/mg) and 44-h exposure period (up to 1000 μg/mg) and the incorporation of an exogenous source of metabolic activation (4-h exposure only). H. parviflora dried powder was non-genotoxic in both in vitro assays. © 2013 Elsevier Ltd.

Ahuja V.,Charite - Medical University of Berlin | Ahuja V.,BSL BIOSERVICE Scientific Laboratories GmbH | Platzek T.,German Federal Institute for Risk Assessment | Fink H.,Free University of Berlin | And 2 more authors.
Archives of Toxicology | Year: 2010

Disperse dyes, which are suitable for dyeing synthetic fibres, are responsible for the great majority of allergic contact dermatitis (ACD) cases to textile dyes. The aim of the present study was to investigate the sensitising potential of various disperse dyes using a biphasic protocol of the local lymph node assay (LLNA). Briefly, mice were shaved over a surface of approximately 2 cm2 on their backs and treated using a "sensitisation-challenge protocol". The shaved surface was treated once daily on days 1-3 with 50 μl of the test solution. Animals remained untreated on days 4-14. On days 15-17, mice were treated with 25 μl of the test solution on the dorsum of both ears. Mice were killed on day 19 with deep CO2 anaesthesia, the lymph nodes prepared and various end points, such as ear thickness, ear punch weight, lymph node weight, lymph node cell count and the proportion of various lymphocyte subpopulations, were determined by flow cytometry. The results were compared to control group treated with the vehicle alone. Our results showed that almost all of the tested textile dyes caused a significant increase in lymph node cell count and lymph node weight. We also observed an increase in ear thickness and ear punch weight in most of the concentrations tested for various textile dyes. We observed a decrease in CD4+ and CD8+ cells and an increase in CD19+, CD45+ and CD45+/1A+ cells in most of the cases, which is characteristic for allergens. The CD4+/CD69+ cells increased in only few experiments mainly with Disperse Blue 124 and Disperse Blue 106. Based on our results, the disperse dyes could be arranged in four groups on the basis of their sensitising potency in the following decreasing order (in parenthesis: lowest concentration causing a significant increase in lymph node cell number): group 1, strong: Disperse Blue 124 and Disperse Blue 106 (0.003%); group 2, moderate: Disperse Red 1 and Disperse Blue 1 (3%); group 3, weak: Disperse Orange 37 and Disperse Blue 35 (10%); and group 4, very weak: Disperse yellow 3 and Disperse Orange 3 (increase at 30% or no increase at 30%). In conclusion, our study shows that the biphasic LLNA protocol was proficient enough to study the sensitisation potential of tested textile dyes and provides data allowing to discriminate them according to their potency. © 2010 Springer-Verlag.

Geletneky K.,University of Heidelberg | Geletneky K.,German Cancer Research Center | Leoni A.-L.,BSL BIOSERVICE Scientific Laboratories GmbH | Pohlmeyer-Esch G.,KALEIDIS Consultancy in Histopathology | And 9 more authors.
Comparative Medicine | Year: 2015

The autonomous parvovirus H1 (H1PV) is transmitted in rodent populations. The natural host is the rat, in which H1PV infection is pathogenic only in fetuses and newborns. H1PV infection of human cancer cells leads to strong oncolytic effects in preclinical models. In preparation for a clinical trial of H1PV injection in patients with malignant brain tumors, H1PV had to be prepared to Good Manufacturing Practice standards, including extensive toxicology testing in rats. Because the trial involves direct intracerebral injection of H1PV into the tumor and around the resection cavity, possible toxicity to CNS tissue had to be investigated. In addition, quantitative blood levels and the tissue distribution of H1PV after single intracerebral or intravenous injection were measured. Direct injection of H1PV into rat brain at 3 dose levels (maximum, 7.96 × 107 pfu) did not cause any macroscopic or histologic pathology. Furthermore, H1PV infection of the brain did not alter central or autonomous nervous system function. H1PV DNA was detected in almost all organs at 6 h, 48 h, and 14 d after intravenous and intracerebral injection, with the highest levels in liver and spleen. H1PV concentrations in most organs were similar after intravenous and intracerebral injection, indicating high permeability of the blood-brain barrier for this small virus. The current results demonstrate wide organ distribution of H1PV after intravenous or intracerebral injection, confirm that H1PV is nonpathogenic in adult rats even after direct injection into the brain, and form the basis for the ongoing ParvOryx01 clinical trial. Copyright 2015 by the American Association for Laboratory Animal Science.

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