| 1. |
- Adamson, L, et al.
(författare)
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Insulin and IGF-1 mediated inhibition of apoptosis in CHO cells grown in suspension in a protein-free medium
- 2007
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Ingår i: Alternatives to laboratory animals : ATLA. - : SAGE Publications. - 0261-1929 .- 2632-3559. ; 35:3, s. 349-352
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Tidskriftsartikel (refereegranskat)abstract
- When Chinese hamster ovary (CHO) cells were grown in suspension and deprived of serum, 40% of them became apoptotic after 72 hours, as determined by flow cytometry analysis of TUNEL-labelled cells. Cell viability, assessed by erythrocin B staining, decreased correspondingly. An increase in the total fraction of cells expressing interleukin converting enzyme (ICE; caspase 1), B-cell lymphoma 2 protein (Bcl-2,) and Bcl-2 associated x protein (Bax) was shown by antibody probing and subsequent flow cytometry. The p53 tumour suppressor gene product level remained low within the cell population. Insulin-like growth factor-1 (IGF-1) inhibited cell death in a concentration-dependent manner, and at 20ng/ml, cell viability was maintained close to 100% and no apoptotic cells were detected. Also, insulin was shown to inhibit cell death — at 1.0μg/ml, cell viability was 95%, whereas 10% of the cells stained for apoptosis. At the highest concentrations of IGF-1 and insulin, the expression of ICE, Bcl-2 and Bax was fully suppressed, whereas the p53 product level increased, despite still being detectable in a minority of cells. Under these conditions, IGF-1 may increase p53 expression to restrain abnormal cell proliferation. It is concluded that special attention should be paid to exposure and culture conditions that induce acquired susceptibility to a toxic insult, during the development and validation of cell-based assays.
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| 2. |
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| 3. |
- Baumans, V
(författare)
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Methods for evaluation of laboratory animal well-being
- 2004
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Ingår i: Alternatives to laboratory animals : ATLA. - : SAGE Publications. - 0261-1929 .- 2632-3559. ; 3232 Suppl 1A, s. 161-162
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Tidskriftsartikel (refereegranskat)abstract
- Well-being is a relative concept, referring to the state of an animal in relation to its ability to cope with its environment. This ability to cope is what we usually try to measure when evaluating the animal's well-being. Good welfare is, in general, considered to be related to a broad behavioural repertoire, which requires a considerable knowledge of the animal's species-specific behaviour and their basic biology. Ideally, well-being should be measured in a positive way, such as measuring pleasure by anticipatory behaviour. However, parameters have more often been designed for detecting failures to cope, leading to stress and/or discomfort. Parameters used in the assessment of discomfort are behavioural parameters, such as stereotypies, reduction in grooming, changes in activity; physiological parameters, such as body weight, abnormal posture, respiratory signs, heart rate, hormone levels; and post-mortem signs, as retrospective parameters, such as stomach ulcers, adrenal cortex size, fatty deposits. The usefulness of these parameters is discussed.
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| 4. |
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| 5. |
- Brandmaier, Stefan, et al.
(författare)
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The QSPR-THESAURUS : The Online Platform of the CADASTER Project
- 2014
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Ingår i: ATLA (Alternatives to Laboratory Animals). - : SAGE Publications. - 0261-1929. ; 42:1, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the CADASTER project (CAse Studies on the Development and Application of in Silico Techniques for Environmental Hazard and Risk Assessment) was to exemplify REACH-related hazard assessments for four classes of chemical compound, namely, polybrominated diphenylethers, per and polyfluorinated compounds, (benzo)triazoles, and musks and fragrances. The QSPR-THESAURUS website (http: / /qspr-thesaurus.eu) was established as the project's online platform to upload, store, apply, and also create, models within the project. We overview the main features of the website, such as model upload, experimental design and hazard assessment to support risk assessment, and integration with other web tools, all of which are essential parts of the QSPR-THESAURUS.
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| 6. |
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| 7. |
- Carbone, L, et al.
(författare)
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Report of the workshop on euthanasia guidelines and practices
- 2004
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Ingår i: Alternatives to laboratory animals : ATLA. - : SAGE Publications. - 0261-1929 .- 2632-3559. ; 3232 Suppl 1B, s. 445-446
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Determining ethical standards for laboratory animal euthanasia requires an assessment of the relative amounts of pain and distress caused by different methods. Animal behaviour data are an important indicator of pain and distress, but their interpretation can be controversial; moreover, behaviour is more easily assessed with some euthanasia methods than with others. While every euthanasia method requires careful study, CO2 inhalation has come under close scrutiny both because it is so widely used for rodent euthanasia, and because it has, until recently, long been considered relatively non-aversive.
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| 8. |
- Cassani, Stefano, et al.
(författare)
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Evaluation of CADASTER QSAR Models for the Aquatic Toxicity of (Benzo)triazoles and Prioritisation by Consensus Prediction
- 2013
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Ingår i: ATLA (Alternatives to Laboratory Animals). - : SAGE Publications. - 0261-1929. ; 41:1, s. 49-64
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Tidskriftsartikel (refereegranskat)abstract
- QSAR regression models of the toxicity of triazoles and benzotriazoles ([B] TAZs) to an alga (Pseudokirchneriella subcapitata), Daphnia magna and a fish (Onchorhynchus mykiss), were developed by five partners in the FP7-EU Project, CADASTER. The models were developed by different methods - Ordinary Least Squares (OLS), Partial Least Squares (PLS), Bayesian regularised regression and Associative Neural Network (ASNN) - by using various molecular descriptors (DRAGON, PaDEL-Descriptor and QSPR-THESAURUS web). In addition, different procedures were used for variable selection, validation and applicability domain inspection. The predictions of the models developed, as well as those obtained in a consensus approach by averaging the data predicted from each model, were compared with the results of experimental tests that were performed by two CADASTER partners. The individual and consensus models were able to correctly predict the toxicity classes of the chemicals tested in the CADASTER project, confirming the utility of the QSAR approach. The models were also used for the prediction of aquatic toxicity of over 300 (B)TAZs, many of which are included in the REACH pre-registration list, and were without experimental data. This highlights the importance of QSAR models for the screening and prioritisation of untested chemicals, in order to reduce and focus experimental testing.
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| 9. |
- Ceder, R, et al.
(författare)
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The application of normal, SV40 T-antigen-immortalised and tumour-derived oral keratinocytes, under serum-free conditions, to the study of the probability of cancer progression as a result of environmental exposure to chemicals
- 2007
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Ingår i: Alternatives to laboratory animals : ATLA. - : SAGE Publications. - 0261-1929 .- 2632-3559. ; 35:6, s. 621-639
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Tidskriftsartikel (refereegranskat)abstract
- In vitro models are currently not considered to be suitable replacements for animals in experiments to assess the multiple factors that underlie the development of cancer as a result of environmental exposure to chemicals. An evaluation was conducted on the potential use of normal keratinocytes, the SV40 T-antigen-immortalised keratinocyte cell line, SVpgC2a, and the carcinoma cell line, SqCC/Y1, alone and in combination, and under standardised serum-free culture conditions, to study oral cancer progression. In addition, features considered to be central to cancer development as a result of environmental exposure to chemicals, were analysed. Genomic expression, and enzymatic and functional data from the cell lines reflected many aspects of the transition of normal tissue epithelium, via dysplasia, to full malignancy. The composite cell line model develops aberrances in proliferation, terminal differentiation and apoptosis, in a similar manner to oral cancer progression in vivo. Transcript and protein profiling links aberrations in multiple gene ontologies, molecular networks and tumour biomarker genes (some proposed previously, and some new) in oral carcinoma development. Typical specific changes include the loss of tumour-suppressor p53 function and of sensitivity to retinoids. Environmental agents associated with the aetiology of oral cancer differ in their requirements for metabolic activation, and cause toxic effects to cells in both the normal and the transformed states. The results suggest that the model might be useful for studies on the sensitivity of cells to chemicals at different stages of cancer progression, including many aspects of the integrated roles of cytotoxicity and genotoxicity. Overall, the properties of the SVpgC2a and SqCC/Y1 cell lines, relative to normal epithelial cells in monolayer or organotypic culture, support their potential applicability to mechanistic studies on cancer risk factors, including, in particular, the definition of critical toxicity effects and dose–effect relationships.
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