The Experts below are selected from a list of 1176 Experts worldwide ranked by ideXlab platform
David Kirkland - One of the best experts on this subject based on the ideXlab platform.
-
cadmium chloride benzo a pyrene and cyclophosphamide tested in the in vitro mammalian cell micronucleus test mnvit in the human lymphoblastoid cell line tk6 at covance laboratories harrogate uk in support of oecd draft test guideline 487
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010Co-Authors: Paul Fowler, James Whitwell, Laura Jeffrey, Jamie Young, Katie Smith, David KirklandAbstract:The following genotoxic chemicals were tested in the in vitro micronucleus assay, at Covance Laboratories, Harrogate, UK in the human lymphoblastoid cell line TK6. Cadmium chloride (an inorganic carcinogen), benzo[a]pyrene (a polycyclic aromatic hydrocarbon requiring metabolic activation) and cyclophosphamide (an alkylating agent requiring metabolic activation) were treated with and without cytokinesis block (by addition of cytochalasin B). This work formed part of a collaborative evaluation of the toxicity measures recommended in the draft OECD Test Guideline 487 for the in vitro micronucleus test. The toxicity measures used, capable of detecting both Cytostasis and cell death, were relative population doubling, relative increase in cell counts and relative cell counts for treatments in the absence of cytokinesis block, and replication index or cytokinesis blocked proliferation index in the presence of cytokinesis block. All of the chemicals tested gave significant increases in the percentage of micronucleated cells with and without cytokinesis block at concentrations giving approximately 60% toxicity (Cytostasis and cell death) or less by all of the toxicity measures used. The outcomes from this series of tests support the use of relative increase in cell counts and relative population doubling, as well as relative cell counts, as appropriate measures of cytotoxicity for the non-cytokinesis blocked in the in vitro micronucleus assay.
-
evaluation of different cytotoxic and cytostatic measures for the in vitro micronucleus test mnvit summary of results in the collaborative trial
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010Co-Authors: David KirklandAbstract:This paper summarises the data for 14 different chemicals tested for induction of micronuclei (MN) in 5 different cell types across 12 different laboratories. All 14 chemicals induced biologically and statistically significant increases in MN frequency in the different cell types (L5178Y, TK6, CHO, CHL, V79) in the absence of cytochalasin B at or below target range toxicity (55+5%) irrespective of whether relative cell count (RCC), relative increase in cell count (RICC) or relative population doubling (RPD) was used as a measure of cytotoxicity/Cytostasis to select the top concentration. All measures of cytotoxicity in the absence of cytochalasin B are therefore considered equally acceptable for use, and the responses were comparable to those obtained in the presence of cytochalasin B.
Klaus Kummerer - One of the best experts on this subject based on the ideXlab platform.
-
chronic ecotoxic effects to pseudomonas putida and vibrio fischeri and cytostatic and genotoxic effects to the hepatoma cell line hepg2 of ofloxacin photo cata lytically treated solutions
Science of The Total Environment, 2013Co-Authors: Marlen I Vasquez, Manuel Garciakaufer, Evroula Hapeshi, Jakob Menz, Konstantinos Kostarelos, Despo Fattakassinos, Klaus KummererAbstract:Ofloxacin (OFL), a broad-spectrum and widespread-used photolabile fluoroquinolone, is frequently found in treated wastewaters, aquatic and terrestrial ecosystems leading to increasing concern during the past decades regarding its effects to the environment and human health. The elimination of OFL and other xenobiotics by the application of advanced oxidation processes using photolytic (PL) and photocatalytic (PC) treatments seems promising. However, an integrated assessment scheme is needed, in which, not only the removal of the parent compound, but also the effects of the photo-transformation products (PTPs) are investigated. For this purpose, in the present study, a chronic ecotoxic assessment using representative bacteria of marine and terrestrial ecosystems and a cytostatic and genotoxic evaluation using hepatoma cell line were performed. PL and PC treatments of OFL were applied using UV radiation. The photo-transformation of OFL during the treatments was monitored by DOC measurements and UPLC–MS/MS analysis. The chronic ecotoxicity of OFL and treated samples was evaluated using Pseudomonas putida and Vibrio fischeri; whereas the Cytostasis and genotoxicity were estimated by the cytokinesis-block micronucleus assay (CBMN). The main results suggest that photo-transformation of OFL took place during these treatments since the concentration of OFL decreased when the irradiation time increased, as quantified by UPLC–MS/MS analysis, and this was not coupled with an analogous DOC removal. Furthermore, nine compounds were identified as probable PTPs formed through piperazinyl dealkylation and decarboxylation. The ecotoxicity of treated solutions to the bacteria studied decreased while the Cytostasis to the hepatoma cell line remained at low levels during both treatments. However, the genotoxicity to the hepatoma cell line demonstrated a different pattern in which treated samples induced a greater number of MNi for the 4–16 min of irradiation (p < 0.05) during both treatments. After 64 min of irradiation, the effects decreased to non genotoxic levels (p < 0.05). These findings suggest that UV radiation for various treatment processes (catalytic or not), such as disinfection, may create genotoxic by-products. Therefore, in relevant technical applications, the residence time during treatment should receive special attention.
Azeddine Elhajouji - One of the best experts on this subject based on the ideXlab platform.
-
mitomycin c 5 fluoruracil colchicine and etoposide tested in the in vitro mammalian cell micronucleus test mnvit in the human lymphoblastoid cell line tk6 at novartis in support of oecd draft test guideline 487
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010Co-Authors: Azeddine ElhajoujiAbstract:The following reference genotoxic agents were tested in the in vitro micronucleus test, at Novartis, Basel, Switzerland. Mitomycin C, 5-fluoruracil, colchicine and etoposide were tested in the human lymphoblastoid cell line TK6, with and without cytokinesis block (in the presence of cytochalasin B). This was done in support of the toxicity measures recommended in the draft OECD Test Guideline on In Vitro Mammalian Cell Micronucleus Test (MNvit) and was part of an international collaborative work. As toxicity measures, detecting Cytostasis and cell death, relative cell counts (RCC), relative increase in cell counts (RICC), and relative population doubling (RPD) were used for treatments in the absence of cytokinesis block, and replication index (RI) or cytokinesis-blocked proliferation in the presence of cytokinesis block. All four reference agents were positive in the assay with and without cytokinesis block at concentrations giving approximately 50% toxicity or less as assessed by all of the toxicity measures used. Accordingly, the results of this work support the use of relative population doubling and relative increase in cell counts, as well as relative cell counts, as appropriate measures of toxicity for the non-cytokinesis-blocked in vitro micronucleus assay.
Mirbahai Ladan - One of the best experts on this subject based on the ideXlab platform.
-
Biomarkers of cell stress and cell death detected by proton high resolution magic angle spinning (\(^1\)H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in a rat glioma cell line
2010Co-Authors: Mirbahai LadanAbstract:Early detection of biomarkers of tumour treatment response improves clinical management, in vivo. Magnetic resonance spectroscopy (MRS) has demonstrated potential for identifying early biomarkers of effective treatment. However, more detailed in vitro studies are required to improve our understanding and facilitate its use. The aim of this study is to determine \(^1\)H high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) biomarkers of Cytostasis and cell death in a rat glioma BT4C cell line. Cytostasis and cell death were induced in BT4C cells using cisplatin and substrate free medium, respectively. Cell viability was examined by various techniques. The lipid and metabolite alterations in whole cells were investigated by \(^1\)H HR-MAS NMR. Significant alterations in lipids and metabolites were detected in response to Cytostasis or necrosis. NMR lipid accumulation was associated with an increase in cytoplasmic lipid droplets seen prior to morphological and molecular markers of cell death. Significant differences were detected in individual choline containing metabolites (CCMs), emphasising the importance of identifying CCMs separately. Alterations were also detected in lactate, alanine, glycine, glutamate, and succinate levels, suggesting changes in the energy metabolism pathways which may provide novel biomarkers in vivo. \(^1\)H HR-MAS NMR reveals alterations in lipids and metabolites during Cytostasis and cell death which may provide early markers of treatment efficacy
-
Biomarkers of cell stress and cell death detected by proton high resolution magic angle spinning (¹H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy in a rat glioma cell line
2010Co-Authors: Mirbahai LadanAbstract:Early detection of biomarkers of tumour treatment response improves clinical management, in vivo. Magnetic resonance spectroscopy (MRS) has demonstrated potential for identifying early biomarkers of effective treatment. However, more detailed in vitro studies are required to improve our understanding and facilitate its use. The aim of this study is to determine ¹H high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) biomarkers of Cytostasis and cell death in a rat glioma BT4C cell line. Cytostasis and cell death were induced in BT4C cells using cisplatin and substrate free medium, respectively. Cell viability was examined by various techniques. The lipid and metabolite alterations in whole cells were investigated by ¹H HR-MAS NMR. Significant alterations in lipids and metabolites were detected in response to Cytostasis or necrosis. NMR lipid accumulation was associated with an increase in cytoplasmic lipid droplets seen prior to morphological and molecular markers of cell death. Significant differences were detected in individual choline containing metabolites (CCMs), emphasising the importance of identifying CCMs separately. Alterations were also detected in lactate, alanine, glycine, glutamate, and succinate levels, suggesting changes in the energy metabolism pathways which may provide novel biomarkers in vivo. ¹H HR-MAS NMR reveals alterations in lipids and metabolites during Cytostasis and cell death which may provide early markers of treatment efficacy.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Marlen I Vasquez - One of the best experts on this subject based on the ideXlab platform.
-
chronic ecotoxic effects to pseudomonas putida and vibrio fischeri and cytostatic and genotoxic effects to the hepatoma cell line hepg2 of ofloxacin photo cata lytically treated solutions
Science of The Total Environment, 2013Co-Authors: Marlen I Vasquez, Manuel Garciakaufer, Evroula Hapeshi, Jakob Menz, Konstantinos Kostarelos, Despo Fattakassinos, Klaus KummererAbstract:Ofloxacin (OFL), a broad-spectrum and widespread-used photolabile fluoroquinolone, is frequently found in treated wastewaters, aquatic and terrestrial ecosystems leading to increasing concern during the past decades regarding its effects to the environment and human health. The elimination of OFL and other xenobiotics by the application of advanced oxidation processes using photolytic (PL) and photocatalytic (PC) treatments seems promising. However, an integrated assessment scheme is needed, in which, not only the removal of the parent compound, but also the effects of the photo-transformation products (PTPs) are investigated. For this purpose, in the present study, a chronic ecotoxic assessment using representative bacteria of marine and terrestrial ecosystems and a cytostatic and genotoxic evaluation using hepatoma cell line were performed. PL and PC treatments of OFL were applied using UV radiation. The photo-transformation of OFL during the treatments was monitored by DOC measurements and UPLC–MS/MS analysis. The chronic ecotoxicity of OFL and treated samples was evaluated using Pseudomonas putida and Vibrio fischeri; whereas the Cytostasis and genotoxicity were estimated by the cytokinesis-block micronucleus assay (CBMN). The main results suggest that photo-transformation of OFL took place during these treatments since the concentration of OFL decreased when the irradiation time increased, as quantified by UPLC–MS/MS analysis, and this was not coupled with an analogous DOC removal. Furthermore, nine compounds were identified as probable PTPs formed through piperazinyl dealkylation and decarboxylation. The ecotoxicity of treated solutions to the bacteria studied decreased while the Cytostasis to the hepatoma cell line remained at low levels during both treatments. However, the genotoxicity to the hepatoma cell line demonstrated a different pattern in which treated samples induced a greater number of MNi for the 4–16 min of irradiation (p < 0.05) during both treatments. After 64 min of irradiation, the effects decreased to non genotoxic levels (p < 0.05). These findings suggest that UV radiation for various treatment processes (catalytic or not), such as disinfection, may create genotoxic by-products. Therefore, in relevant technical applications, the residence time during treatment should receive special attention.
