| 1. |
- Vandenberg, Laura N., et al.
(författare)
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A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals
- 2016
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Ingår i: Environmental Health. - London : BioMed Central (BMC). - 1476-069X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs.Methods: We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity.Results: Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs.Conclusions: When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.
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| 2. |
- Cotgreave, Ian A, et al.
(författare)
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Differentiation-specific alterations to glutathione synthesis in and hormonally stimulated release from human skeletal muscle cells.
- 2002
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 16:3, s. 435-7
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Tidskriftsartikel (refereegranskat)abstract
- Muscle atrophy and cachexia are associated with many human diseases. These catabolic states are often associated with the loss of glutathione (GSH), which is thought to contribute to the induction of oxidative stress within the muscle. Glutathione synthesis and secretary characteristics were studied in human skeletal muscle myoblasts and myotube-like cells derived from the myoblasts by growth factor restriction. Differentiation was associated with a shift in the sulfur amino acid precursor specificity for synthesis of GSH from cystine to cysteine, as well as loss in ability to use extracellular glutathione and activation of methionine use. The thiol drug N-acetylcysteine was also shown to be an effective precursor irrespective of the state of differentiation. Additionally, myoblasts and myotube cultures were shown to secrete GSH continually, but only the differentiated cells responded to stress hormones such as glucagon, vasopressin, and phenylephrine, by increased secretion of the tripeptide. The data suggest that the skeletal muscle cells may provide an important hormonally regulated extra-hepatic source of systemic GSH and also shed light on the mechanisms of accelerated turnover of GSH operating during strenuous muscle activity and trauma. The data may also provide biochemical rationales for the nutritional and/or pharmacological manipulation of GSH with sulfur amino acid precursors during the treatment of muscle-specific oxidative stress and atrophy.
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| 3. |
- Dahllöf, Lisbeth, et al.
(författare)
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The application of a tiered life cycle assessment (LCA) approach to safe and sustainable chemistry in the development of smart solutions for water and air purification: The Mistra TerraClean case
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In the Swedish research programme Mistra TerraClean a tiered approach for life cycle based environmental and human health assessment early in process development was introduced. In the project smart filters for water and air purification are under development. Innovative materials and devices are applied and evaluated with a systems perspective. In our tiered approach life cycle assessment (LCA), chemical safety assessment and applied eco and human toxicity assessments are combined, with a particular focus on the inclusion of toxicity potential impacts in LCA.To this end, the consensus model USEtox has been applied, complemented with the method ProScale, that focusses on human direct exposure. The life cycle-based approach has so far been applied to material development and a pilot scale case study. The case study focuses on water purification of per- and polyfluoroalkyl substances (PFAS) for which we have a PFAS adapted life cycle impact assessment framework at hand. This tiered approach is relevant to process developers, people within the field of water and air treatment as well as the broader LCA community.
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| 4. |
- Garberg, Per, et al.
(författare)
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Binding of tellurium to hepatocellular selenoproteins during incubationwith inorganic tellurite : consequences for the activity ofselenium-dependent glutathione peroxidase
- 1999
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Ingår i: International Journal of Biochemistry and Cell Biology. - 1357-2725 .- 1878-5875. ; 31:2, s. 291-301
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Tidskriftsartikel (refereegranskat)abstract
- The metallic group XVIa elements selenium and tellurium possess remarkably similar chemical properties. However, unlike selenium, tellurium is not an essential micronutrient and, indeed, induces both acute and chronic toxicity in a variety of species. Despite this, very little is known of the molecular mechanisms of toxicity of tellurium, particularly with respect to potential chemical interactions with selenium-containing components in the cell. In this work we describe a novel interaction of inorganic tellurite with hepatocellular selenoproteins, particularly with selenium-dependent glutathione peroxidase. The accumulation of (121Te)-tellurite into cultured primary rat liver hepatocytes was shown to be much more rapid than that of (75Se)-selenite on a molar basis. Neither the uptake of (121Te)-tellurite nor of (75Se)-selenite was affected by a large molar excess of the unlabelled counterpart, respectively. Interestingly, separation of the hepatocellular proteins on continuous pH denaturing gels demonstrated clear binding of radiolabelled tellurium to a number of protein bands, including one at 23 and one at 58 kDa, which corresponded to proteins readily labelled in cells treated with (75Se)-selenite. The binding of (121Te) to these proteins was insensitive to reduction with mercaptoethanol and not affected by pre-treatment of the cells with cycloheximide. When purified selenium-dependent glutathione peroxidase was treated directly with (121Te)-tellurite, the protein became labelled in an analogous manner to that achieved in intact cells. This was not affected by coincubation of the enzyme with (121Te)-tellurite and one or both of its substrates. Additionally, incubation of the peroxidase with tellurite effectively inhibited its ability to catalyse glutathione-dependent reduction of hydrogen peroxide. These data suggest that inorganic tellurite delivers tellurium to the intracellular milieu in a form capable of binding to some intracellular selenoproteins and at least in the case of glutathione peroxidase, cause inhibition of catalytic activity. The nature of the binding seems not to be due to the insertion of tellurocysteine into the protein and the insensitivity to reductive cleavage with mercaptoethanol seems to preclude the formation of stable telluro-selenides in the proteins. These data may offer alternative explanations for the established toxicity of tellurium via disruption of selenoprotein function, particularly by the induction of intracellular oxidative stress by the inhibition of Se-dependent glutathione peroxidase.
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| 5. |
- Mattsson, Ase, et al.
(författare)
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H2AX phosphorylation in A549 cells induced by the bulky and stable DNA adducts of benzo[a]pyrene and dibenzo[a,l]pyrene diol epoxides
- 2009
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Ingår i: Chemico-Biological Interactions. - : Elsevier BV. - 0009-2797 .- 1872-7786. ; 177:1, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- Early events in the cellular response to DNA damage, such as double strand breaks, rely on lesion recognition and activation of proteins involved in maintenance of genomic stability. One important component of this process is the phosphorylation of the histone variant H2AX. To investigate factors explaining the variation in carcinogenic potency between different categories of polycyclic aromatic hydrocarbons (PAHs). we have studied the phosphorylation of H2AX (H2AX gamma). A549 cells were exposed to benzo[a]pyrene diol epoxide [(+)-anti-BPDE] (a bay-region PAH) and dibenzo[a,l]pyrene diol epoxide [(-)-anti-DBPDE] (a fjord-region PAH) and H2AX gamma was studied using immunocytochemistry and Western blot. Hydrogen peroxide (H2O2) was used to induce oxidative DNA damage and strand breaks. As showed with single cell gel electrophoresis, neither of the diol epoxides resulted in DNA strand breaks relative to H2O2. Visualisation of H(2)AX gamma formation demonstrated that the proportion of cells exhibiting H2AX gamma staining at 1 h differed between BPDE, 40% followed by a decline, and DBPDE, <10% followed by an increase. With H2O2 treatment, almost all cells demonstrated H(2)AX gamma at 1 h. Western blot analysis of the H2AX gamma formation also showed concentration and time-dependent response patterns. The kinetics of H2AX gamma formation correlated with the previously observed kinetics of elimination of BPDE and DBPDE adducts. Thus, the extent of H2AX gamma formation and persistence was related to both the number of adducts and their structural features.
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