41 results on '"MAURICI Daniela"'
Search Results
2. Guidance on aneugenicity assessment
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EFSA Scientific Committee (SC), More, Simon John, Bampidis, Vasileios, Bragard, Claude, Halldorsson, Thorhallur Ingi, Hernández-Jerez, Antonio F, Hougaard Bennekou, Susanne, Koutsoumanis, Kostas, Lambré, Claude, Machera, Kyriaki, Naegeli, Hanspeter, Nielsen, Søren Saxmose, Schlatter, Josef, Schrenk, Dieter, Turck, Dominique, Younes, Maged, Aquilina, Gabriele, Bignami, Margherita, Bolognesi, Claudia, Crebelli, Riccardo, Gürtler, Rainer, Marcon, Francesca, Nielsen, Elsa, Vleminckx, Christiane, Carfì, Maria, Martino, Carla, Maurici, Daniela, Parra Morte, Juan, Rossi, Annamaria, Benford, Diane, and University of Zurich
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Veterinary (miscellaneous) ,Aneugenicity ,2405 Parasitology ,TP1-1185 ,Genotoxicity in vivo and in vitro ,Plant Science ,Gene mutation ,Bioinformatics ,Microbiology ,Clastogen ,In vitro ,Micronucleus test ,1110 Plant Science ,In vivo ,medicine ,TX341-641 ,1106 Food Science ,Nutrition. Foods and food supply ,business.industry ,Chemical technology ,Cros1223 ,genotoxicity in vivo and in vitro ,2404 Microbiology ,10079 Institute of Veterinary Pharmacology and Toxicology ,aneugenicity ,3401 Veterinary (miscellaneous) ,micronucleus test ,Scientific Opinion ,medicine.anatomical_structure ,570 Life sciences ,biology ,Animal Science and Zoology ,Parasitology ,Bone marrow ,1103 Animal Science and Zoology ,Genotoxicity ,business ,Risk assessment ,Food Science - Abstract
The EFSA Scientific Committee was asked to provide guidance on the most appropriate in vivo tests to follow up on positive in vitro results for aneugenicity, and on the approach to risk assessment for substances that are aneugenic but not clastogenic nor causing gene mutations. The Scientific Committee confirmed that the preferred approach is to perform an in vivo mammalian erythrocyte micronucleus test with a relevant route of administration. If this is positive, it demonstrates that the substance is aneugenic in vivo. A negative result with evidence that the bone marrow is exposed to the test substance supports a conclusion that aneugenic activity is not expressed in vivo. If there is no evidence of exposure to the bone marrow, a negative result is viewed as inconclusive and further studies are required. The liver micronucleus assay, even though not yet fully validated, can provide supporting information for substances that are aneugenic following metabolic activation. The gastrointestinal micronucleus test, conversely, to be further developed, may help to assess aneugenic potential at the initial site of contact for substances that are aneugenic in vitro without metabolic activation. Based on the evidence in relation to mechanisms of aneugenicity, the Scientific Committee concluded that, in principle, health‐based guidance values can be established for substances that are aneugenic but not clastogenic nor causing gene mutations, provided that a comprehensive toxicological database is available. For situations in which the toxicological database is not sufficient to establish health‐based guidance values, some approaches to risk assessment are proposed. The Scientific Committee recommends further development of the gastrointestinal micronucleus test, and research to improve the understanding of aneugenicity to support risk assessment., This publication is linked to the following EFSA Supporting Publications article: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2021.EN-6814/full
- Published
- 2021
3. Guidance on aneugenicity assessment
- Author
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EFSA Scientific Committee, More, Simon John, Bampidis, Vasileios, Bragard, Claude, Halldorsson, Thorhallur Ingi, Hernández-Jerez, Antonio F, Hougaard Bennekou, Susanne, Koutsoumanis, Kostas, Lambré, Claude, Machera, Kyriaki, Naegeli, Hanspeter, Nielsen, Søren Saxmose, Schlatter, Josef, Schrenk, Dieter, Turck, Dominique, Younes, Maged, Aquilina, Gabriele, Bignami, Margherita, Bolognesi, Claudia, Crebelli, Riccardo, Gürtler, Rainer, Marcon, Francesca, Nielsen, Elsa, Vleminckx, Christiane, Carfì, Maria, Martino, Carla, Maurici, Daniela, Parra Morte, Juan, Rossi, Annamaria, Benford, Diane, EFSA Scientific Committee, More, Simon John, Bampidis, Vasileios, Bragard, Claude, Halldorsson, Thorhallur Ingi, Hernández-Jerez, Antonio F, Hougaard Bennekou, Susanne, Koutsoumanis, Kostas, Lambré, Claude, Machera, Kyriaki, Naegeli, Hanspeter, Nielsen, Søren Saxmose, Schlatter, Josef, Schrenk, Dieter, Turck, Dominique, Younes, Maged, Aquilina, Gabriele, Bignami, Margherita, Bolognesi, Claudia, Crebelli, Riccardo, Gürtler, Rainer, Marcon, Francesca, Nielsen, Elsa, Vleminckx, Christiane, Carfì, Maria, Martino, Carla, Maurici, Daniela, Parra Morte, Juan, Rossi, Annamaria, and Benford, Diane
- Abstract
The EFSA Scientific Committee was asked to provide guidance on the most appropriate in vivo tests to follow up on positive in vitro results for aneugenicity, and on the approach to risk assessment for substances that are aneugenic but not clastogenic nor causing gene mutations. The Scientific Committee confirmed that the preferred approach is to perform an in vivo mammalian erythrocyte micronucleus test with a relevant route of administration. If this is positive, it demonstrates that the substance is aneugenic in vivo. A negative result with evidence that the bone marrow is exposed to the test substance supports a conclusion that aneugenic activity is not expressed in vivo. If there is no evidence of exposure to the bone marrow, a negative result is viewed as inconclusive and further studies are required. The liver micronucleus assay, even though not yet fully validated, can provide supporting information for substances that are aneugenic following metabolic activation. The gastrointestinal micronucleus test, conversely, to be further developed, may help to assess aneugenic potential at the initial site of contact for substances that are aneugenic in vitro without metabolic activation. Based on the evidence in relation to mechanisms of aneugenicity, the Scientific Committee concluded that, in principle, health-based guidance values can be established for substances that are aneugenic but not clastogenic nor causing gene mutations, provided that a comprehensive toxicological database is available. For situations in which the toxicological database is not sufficient to establish health-based guidance values, some approaches to risk assessment are proposed. The Scientific Committee recommends further development of the gastrointestinal micronucleus test, and research to improve the understanding of aneugenicity to support risk assessment.
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- 2021
4. How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary follow-up animal tests: Report of an ECVAM Workshop
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Kirkland, David, Pfuhler, Stefan, Tweats, David, Aardema, Marilyn, Corvi, Raffaella, Darroudi, Firouz, Elhajouji, Azeddine, Glatt, Hansruedi, Hastwell, Paul, Hayashi, Makoto, Kasper, Peter, Kirchner, Stephan, Lynch, Anthony, Marzin, Daniel, Maurici, Daniela, Meunier, Jean-Roc, Müller, Lutz, Nohynek, Gerhard, Parry, James, Parry, Elizabeth, Thybaud, Veronique, Tice, Ray, van Benthem, Jan, Vanparys, Philippe, and White, Paul
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- 2007
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5. Amifostine (WR2721) restores transcriptional activity of specific p53 mutant proteins in a yeast functional assay
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Maurici, Daniela, Monti, Paola, Campomenosi, Paola, North, Sophie, Frebourg, Thierry, Fronza, Gilberto, and Hainaut, Pierre
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- 2001
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6. The expression of P-glycoprotein is causally related to a less aggressive phenotype in human osteosarcoma cells
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Scotlandi, Katia, Manara, Maria Cristina, Serra, Massimo, Benini, Stefania, Maurici, Daniela, Caputo, Antonella, De Giovanni, Carla, Lollini, Pier-Luigi, Nanni, Patrizia, Picci, Piero, Campanacci, Mario, and Baldini, Nicola
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- 1999
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7. Editorial: Exploring the need to include microbiomes into EFSA's scientific assessments
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Merten, Caroline, primary, Schoonjans, Reinhilde, additional, Di Gioia, Diana, additional, Peláez, Carmen, additional, Sanz, Yolanda, additional, Maurici, Daniela, additional, and Robinson, Tobin, additional
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- 2020
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8. ECVAM retrospective validation of in vitro micronucleus test (MNT)
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Corvi, Raffaella, Albertini, Silvio, Hartung, Thomas, Hoffmann, Sebastian, Maurici, Daniela, Pfuhler, Stefan, van Benthem, Jan, and Vanparys, Philippe
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- 2008
9. Evaluation of P-glycoprotein expression in soft tissue sarcomas of the extremities
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Serra, Massimo, Scotlandi, Katia, Manara, Maria Cristina, Maurici, Daniela, Benini, Stefania, Sarti, Manuela, Nini, Giuseppe, Barbanti-Brodano, Giovanni, and Baldini, Nicola
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- 1996
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10. Genotoxicity assessment of chemical mixtures
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More, Simon, Bampidis, Vasileios, Benford, Diane, Boesten, Jos, Bragard, Claude, Halldorsson, Thorhallur, Hernandez‐Jerez, Antonio, Hougaard‐Bennekou, Susanne, Koutsoumanis, Kostas, Naegeli, Hanspeter; https://orcid.org/0000-0001-5762-1359, Nielsen, Søren Saxmose, Schrenk, Dieter, Silano, Vittorio, Turck, Dominique, Younes, Maged, Aquilina, Gabriele, Crebelli, Riccardo, Gürtler, Rainer, Hirsch‐Ernst, Karen Ildico, Mosesso, Pasquale, Nielsen, Elsa, Solecki, Roland, Carfì, Maria, Martino, Carla, Maurici, Daniela, Parra Morte, Juan, Schlatter, Josef, More, Simon, Bampidis, Vasileios, Benford, Diane, Boesten, Jos, Bragard, Claude, Halldorsson, Thorhallur, Hernandez‐Jerez, Antonio, Hougaard‐Bennekou, Susanne, Koutsoumanis, Kostas, Naegeli, Hanspeter; https://orcid.org/0000-0001-5762-1359, Nielsen, Søren Saxmose, Schrenk, Dieter, Silano, Vittorio, Turck, Dominique, Younes, Maged, Aquilina, Gabriele, Crebelli, Riccardo, Gürtler, Rainer, Hirsch‐Ernst, Karen Ildico, Mosesso, Pasquale, Nielsen, Elsa, Solecki, Roland, Carfì, Maria, Martino, Carla, Maurici, Daniela, Parra Morte, Juan, and Schlatter, Josef
- Abstract
The EFSA Scientific Committee addressed in this document the peculiarities related to the genotoxicity assessment of chemical mixtures. The EFSA Scientific Committee suggests that first a mixture should be chemically characterised as far as possible. Although the characterisation of mixtures is relevant also for other toxicity aspects, it is particularly significant for the assessment of genotoxicity. If a mixture contains one or more chemical substances that are individually assessed to be genotoxic in vivo via a relevant route of administration, the mixture raises concern for genotoxicity. If a fully chemically defined mixture does not contain genotoxic chemical substances, the mixture is of no concern with respect to genotoxicity. If a mixture contains a fraction of chemical substances that have not been chemically identified, experimental testing of the unidentified fraction should be considered as the first option or, if this is not feasible, testing of the whole mixture should be undertaken. If testing of these fraction(s) or of the whole mixture in an adequately performed set of in vitro assays provides clearly negative results, the mixture does not raise concern for genotoxicity. If in vitro testing provides one or more positive results, an in vivo follow‐up study should be considered. For negative results in the in vivo follow‐up test(s), the possible limitations of in vivo testing should be weighed in an uncertainty analysis before reaching a conclusion of no concern with respect to genotoxicity. For positive results in the in vivo follow‐up test(s), it can be concluded that the mixture does raise a concern about genotoxicity.
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- 2019
11. Adriamycin binding assay: a valuable chemosensitivity test in human osteosarcoma
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Baldini, Nicola, Scotlandi, Katia, Serra, Massimo, Kusuzaki, Katsuyuki, Shikita, Toshiharu, Manara, Maria C., Maurici, Daniela, and Campanacci, Mario
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- 1992
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12. Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome
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Baldini, Nicola, Scotlandi, Katia, Barbanti-Brodano, Giovanni, Manara, Maria Cristina, Maurici, Daniela, Bacci, Gaetano, Bertoni, Franco, Picci, Piero, Sottili, Sandra, Campanacci, Mario, and Serra, Massimo
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Osteosarcoma -- Prognosis ,Glycoproteins -- Physiological aspects - Abstract
High levels of P-glycoprotein in tumor cells of osteosarcoma appear to increase the risk of tumor relapse or death following surgery and chemotherapy. Osteosarcoma is a bone tumor that is often cancerous. Researchers studied the levels of the membrane pump P-glycoprotein in tumor cells of 92 patients with osteosarcoma who had surgery and chemotherapy. In 28 (30%) of the tumors, P-glycoprotein appeared at elevated levels in cells throughout the tumor. Tumors located at the end of bones closer to the torso tended to have higher P-glycoprotein levels. During a minimum follow-up of 63 months, the rate of tumor relapse or death during remission was 3.4 times higher in people with high P-glycoprotein levels. Poor response to chemotherapy also appeared to increase the likelihood of a poor outcome.
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- 1995
13. Implementation of PROMETHEUS 4‐step approach for evidence use in EFSA scientific assessments: benefits, issues, needs and solutions
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Aiassa, Elisa, Martino, Laura, Barizzone, Fulvio, Ciccolallo, Laura, Garcia, Ana, Georgiadis, Marios, Guajardo, Irene Muñoz, Tomcikova, Daniela, Alexander, Jan, Calistri, Paolo, Gundert‐remy, Ursula, Hart, Andrew David, Hoogenboom, Ron Laurentius, Messean, Antoine, Naska, Androniki, Navarro, Maria Navajas, Noerrung, Birgit, Ockleford, Colin, Wallace, Robert John, Younes, Maged, Abuntori, Blaize, Alvarez, Fernando, Aryeetey, Monica, Baldinelli, Francesca, Barrucci, Federica, Bau, Andrea, Binaglia, Marco, Broglia, Alessandro, Castoldi, Anna Federica, Christoph, Eugen, De Sesmaisons‐Lecarré, Agnes, Georgiadis, Nikolaos, Gervelmeyer, Andrea, Istace, Frederique, López‐Gálvez, Gloria, Manini, Paola, Maurici, Daniela, Merten, Caroline, Messens, Winy, Mosbach‐Schulz, Olaf, Putzu, Claudio, Bordajandi, Luisa Ramos, Smeraldi, Camilla, Tiramani, Manuela, Martínez, Silvia Valtueña, Sybren, Vos, Hardy, Anthony Richard, Hugas, Marta, Kleiner, Juliane, Seze, Guilhem De, Aiassa, Elisa, Martino, Laura, Barizzone, Fulvio, Ciccolallo, Laura, Garcia, Ana, Georgiadis, Marios, Guajardo, Irene Muñoz, Tomcikova, Daniela, Alexander, Jan, Calistri, Paolo, Gundert‐remy, Ursula, Hart, Andrew David, Hoogenboom, Ron Laurentius, Messean, Antoine, Naska, Androniki, Navarro, Maria Navajas, Noerrung, Birgit, Ockleford, Colin, Wallace, Robert John, Younes, Maged, Abuntori, Blaize, Alvarez, Fernando, Aryeetey, Monica, Baldinelli, Francesca, Barrucci, Federica, Bau, Andrea, Binaglia, Marco, Broglia, Alessandro, Castoldi, Anna Federica, Christoph, Eugen, De Sesmaisons‐Lecarré, Agnes, Georgiadis, Nikolaos, Gervelmeyer, Andrea, Istace, Frederique, López‐Gálvez, Gloria, Manini, Paola, Maurici, Daniela, Merten, Caroline, Messens, Winy, Mosbach‐Schulz, Olaf, Putzu, Claudio, Bordajandi, Luisa Ramos, Smeraldi, Camilla, Tiramani, Manuela, Martínez, Silvia Valtueña, Sybren, Vos, Hardy, Anthony Richard, Hugas, Marta, Kleiner, Juliane, and Seze, Guilhem De
- Abstract
In 2014, the European Food Safety Authority (EFSA) started the PROMETHEUS (PROmoting METHods for Evidence Use in Scientific assessments) project to improve further and increase the consistency of the methods it uses in its scientific assessments. The project defined a set of principles for the scientific assessment process and a 4‐step approach (plan/carry out/verify/report) for their fulfilment, which was tested in ten case studies, one from each EFSA panel. The present report describes the benefits, issues, needs and solutions related to the implementation of the 4‐step approach in EFSA, identified in a dedicated workshop in October 2017. The key benefits of the approach, which was deemed applicable to all types of EFSA scientific assessment including assessments of regulated products, are: 1) increased ‘scientific value’ of EFSA outputs, i.e. the extent of impartiality, methodological rigour, transparency and engagement; 2) guarantee of fitness‐for‐purpose, as it implies tailoring the methods to the specificities of each assessment; 3) efficiency gain, since preparing a protocol for the assessment upfront helps more streamlined processes throughout the implementation phase; 4) innovation, as the approach promotes the pioneering practice of ‘planning before doing’ (well established in primary research) for broad scientific assessments in regulatory science; and 5) increased harmonisation and consistency of EFSA assessments. The 4‐step approach was also considered an effective system for detecting additional methodological and/or expertise needs and a useful basis for further defining a quality management system for EFSA's scientific processes. The identified issues and solutions related to the implementation of the approach are: a) lack of engagement and need for effective communication on benefits and added value; b) need for further advances especially in the field of problem formulation/protocol development, evidence appraisal and evidence integration; c) need
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- 2018
14. Clinical relevance of Ki-67 expression in bone tumors
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Scotlandi, Katia, Serra, Massimo, Manara, M. Cristina, Maurici, Daniela, Benini, Stefania, Nini, Giuseppe, Campanacci, Mario, and Baldini, Nicola
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Bone tumors -- Prognosis ,Gene expression -- Physiological aspects ,Health - Abstract
Background. The availability of Ki-67 monoclonal antibody has opened new possibilities for an extensive analysis of cell kinetics in human neoplasms. Ki-67 antibody reveals a nuclear antigen that is expressed in proliferating but not in quiescent cells. Although the reliability of Ki-67 immunostaining has been evaluated in different tumor types, little information has been reported on bone neoplasms. Methods. Cell proliferation, as determined by Ki-67 expression, was measured by immunofluorescence on representative cytospins obtained from 205 patients with bone tumors. In each sample, the percentage of Ki-67-positive cells was quantified on at least 500 cells and expressed as Ki-67 labeling index (LI). Results. Ki-67 LI was lower in benign and low grade lesions as compared with high grade malignant lesions. A correlation between Ki-67 LI and histologic grade was observed in osteosarcoma and chondrosarcoma. In osteosarcoma, among the 43 primary lesions included in this study, 30 patients, all treated with the same regimen of chemotherapy and limb-salvage surgery, were selected to establish the prognostic significance of cell proliferation. The Ki-67 labeling was higher in patients with a good histologic response to chemotherapy. However, at a 24-month follow-up, a worse prognosis was associated with a higher proliferative activity, whereas no correspondence was found between the histologic response to preoperative chemotherapy and the disease free survival, suggesting that in high grade osteosarcoma the biologic aggressiveness expressed by high levels of Ki-67 LI may be clinically more relevant than the responsiveness to antineoplastic agents. Conclusions. In bone tumors, the level of Ki-67 expression correlates with the level of malignancy and is diagnostically and prognostically useful.
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- 1995
15. Scientific motivations and criteria to consider updating EFSA scientific assessments
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Hardy, Anthony, Benford, Diane, Halldorsson, Thorhallur, Jeger, Michael John, Knutsen, Katrine Helle, More, Simon, Mortensen, Alicja, Naegeli, Hanspeter, Noteborn, Hubert, Ockleford, Colin, Ricci, Antonia, Rychen, Guido, Schlatter, Josep R., Silano, Vittorio, Solecki, Roland, Turck, Dominique, Brock, Theo, Chesson, Andrew, Karenlampi, Sirpa, Lambre, Claude, Sanz, Yolande, Goumperis, Tilemachos, Kleiner, Juliane, Maurici, Daniela, Hardy, Anthony, Benford, Diane, Halldorsson, Thorhallur, Jeger, Michael John, Knutsen, Katrine Helle, More, Simon, Mortensen, Alicja, Naegeli, Hanspeter, Noteborn, Hubert, Ockleford, Colin, Ricci, Antonia, Rychen, Guido, Schlatter, Josep R., Silano, Vittorio, Solecki, Roland, Turck, Dominique, Brock, Theo, Chesson, Andrew, Karenlampi, Sirpa, Lambre, Claude, Sanz, Yolande, Goumperis, Tilemachos, Kleiner, Juliane, and Maurici, Daniela
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EFSA is committed to assess and communicate the risks occurring in the food and feed chain from farm to fork and to provide other forms of scientific advice. This work, carried out by EFSA since its inception, has resulted in the adoption of thousands of scientific assessments. EFSA is obliged to re-assess past assessments in specific regulatory contexts such as those on food and feed additives, active substances in plant protection products and genetically modified food and feed. In other sectors, the consideration for updating past EFSA scientific assessments is taken on an ad hoc basis mainly depending on specific requests by risk managers or on EFSA self-tasking. If safety is potentially at stake in any area within EFSA's remit, the readiness to update past scientific assessments is important to keep EFSA at the forefront of science and to promote an effective risk assessment. Although this task might be very complex and resource demanding, it is fundamental to EFSA's mission. The present EFSA Scientific Committee opinion deals with scientific motivations and criteria to contribute to the timely updating of EFSA scientific assessments. It is recognised that the decision for updating should be agreed following careful consideration of all the relevant elements by the EFSA management, in collaboration with risk managers and stakeholders. The present opinion addresses the scientific approaches through which it would be possible for EFSA to increase the speed and effectiveness of the acquisition of new data, as well as, to improve the consequent evaluations to assess the relevance and reliability of new data in the context of contributing to the better definition of whether to update past scientific assessments.
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- 2017
16. Clarification of some aspects related to genotoxicity assessment
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Hardy, Anthony, Benford, Diane, Halldorsson, Thorhallur, Jeger, Michael, Knutsen, Helle Katrine, More, Simon, Naegeli, Hanspeter, Noteborn, Hubert, Ockleford, Colin, Ricci, Antonia, Rychen, Guido, Silano, Vittorio, Solecki, Roland, Turck, Dominique, Younes, Maged, Aquilina, Gabriele, Crebelli, Riccardo, Gürtler, Rainer, Hirsch-Ernst, Karen Ildico, Mosesso, Pasquale, Nielsen, Elsa, van Benthem, Jan, Carfì, Maria, Georgiadis, Nikolaos, Maurici, Daniela, Parra Morte, Juan, Schlatter, Josef, Hardy, Anthony, Benford, Diane, Halldorsson, Thorhallur, Jeger, Michael, Knutsen, Helle Katrine, More, Simon, Naegeli, Hanspeter, Noteborn, Hubert, Ockleford, Colin, Ricci, Antonia, Rychen, Guido, Silano, Vittorio, Solecki, Roland, Turck, Dominique, Younes, Maged, Aquilina, Gabriele, Crebelli, Riccardo, Gürtler, Rainer, Hirsch-Ernst, Karen Ildico, Mosesso, Pasquale, Nielsen, Elsa, van Benthem, Jan, Carfì, Maria, Georgiadis, Nikolaos, Maurici, Daniela, Parra Morte, Juan, and Schlatter, Josef
- Abstract
The European Commission requested EFSA to provide advice on the following: (1) the suitability of the unscheduled DNA synthesis (UDS) in vivo assay to follow-up positive results in in vitro gene mutation tests; (2) the adequacy to demonstrate target tissue exposure in in vivo studies, particularly in the mammalian erythrocyte micronucleus test; (3) the use of data in a weight-of-evidence approach to conclude on the genotoxic potential of substances and the consequent setting of health-based guidance values. The Scientific Committee concluded that the first question should be addressed in both a retrospective and a prospective way: for future assessments, it is recommended no longer performing the UDS test. For re-assessments, if the outcome of the UDS is negative, the reliability and significance of results should be carefully evaluated in a weight-of-evidence approach, before deciding whether more sensitive tests such as transgenic assay or in vivo comet assay would be needed to complete the assessment. Regarding the second question, the Scientific Committee concluded that it should be addressed in lines of evidence of bone marrow exposure: toxicity to the bone marrow in itself provides sufficient evidence to allow concluding on the validity of a negative outcome of a study. All other lines of evidence of target tissue exposure should be assessed within a weight-of-evidence approach. Regarding the third question, the Scientific Committee concluded that any available data that may assist in reducing the uncertainty in the assessment of the genotoxic potential of a substance should be taken into consideration. If the overall evaluation leaves no concerns for genotoxicity, health-based guidance values may be established. However, if concerns for genotoxicity remain, establishing health-based guidance values is not considered appropriate.
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- 2017
17. Genotoxicity testing approaches for the safety assessment of substances used in food contact materials prior to their authorization in the European Union
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Bolognesi, Claudia, primary, Castoldi, Anna F., additional, Crebelli, Riccardo, additional, Barthélémy, Eric, additional, Maurici, Daniela, additional, Wölfle, Detlef, additional, Volk, Katharina, additional, and Castle, Laurence, additional
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- 2017
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18. EFSA cross‐cutting guidance lifecycle.
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European Food Safety Authority (EFSA), Maurici, Daniela, Garcia Matas, Raquel, and Gervelmeyer, Andrea
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This document describes the lifecycle of cross‐cutting guidance documents in EFSA. Cross‐cutting guidance documents deal with matters of a horizontal nature in fields that affect scientific areas covered by more than one Panel. The main objective of developing cross‐cutting guidance documents is to harmonise food and feed safety risk assessment in EFSA. The document outlines the procedures for the identification of needs for cross‐cutting guidance documents, their development, implementation, their review and revision. [ABSTRACT FROM AUTHOR]
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- 2018
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19. Validation of Toxicogenomics-Based Test Systems:ECVAM-ICCVAM/NICEATM Considerations for Regulatory Use
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CORVI RAFFAELLA, AHR Hans, ALBERTINI Silvio, BLAKEY David, CLERICI Libero, COECKE SANDRA, DOUGLAS George, GRIBALDO LAURA, GROTEN John, HAASE Bernd, HAMERNIK Karen, HARTUNG THOMAS, INOUE Tohru, INDANS Ian, MAURICI Daniela, ORPHANIDES George, REMBGES DIANA, SANSONE Susanna, SNAPE Jason, TODA Eisaku, TONG Weida, VAN DELFT Joost, WEIS Brenda, and SCHECHTMAN Leonard
- Abstract
This is the report of the first workshop on the Validation of Toxicogenomics-based Test Systems held in Ispra, Italy on 11-12 December 2003. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and organized jointly by ECVAM, the U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). The primary aim of the workshop was to discuss and define principles applicable to the validation of toxicogenomics platforms as well as validation of specific toxicological test methods that incorporate toxicogenomics technologies. The workshop was viewed as an opportunity for initiating a dialogue between technological experts, regulators, and the principal validation bodies, and for identifying those factors to which the validation process would be applicable. It was felt that to do so now, as the technology is evolving and associated challenges are identified, would serve as the basis for the future validation of the technology when it reached the appropriate stage. Due to the complexity of the issue, different aspects of the validation of toxicogenomics-based test methods were covered. The three focus areas included (a) biological validation of toxicogenomics-based test methods for regulatory decision-making, (b) technical and bioinformatics aspects related to validation, and (c) validation issues as they relate to regulatory acceptance and utilization of toxicogenomics-based test methods. This report summarizes the discussions and details the recommendations for future direction and priorities., JRC.I.2-Validation of biomedical testing methods
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- 2005
20. Modulation of different stress pathways after styrene and styrene-7,8-oxide exposure in HepG2 cell line and normal human hepatocytes
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Diodovich, Cristina, primary, Urani, Chiara, additional, Maurici, Daniela, additional, Malerba, Ilaria, additional, Melchioretto, Pasquale, additional, Orlandi, Marco, additional, Zoia, Luca, additional, Campi, Valentina, additional, Carfi', Maria, additional, Pellizzer, Cristian, additional, and Gribaldo, Laura, additional
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- 2006
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21. 3.7. Genotoxicity and Mutagenicity
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Maurici, Daniela, primary, Aardema, Marilyn, additional, Corvi, Raffaella, additional, Kleber, Marcus, additional, Krul, Cyrille, additional, Laurent, Christian, additional, Loprieno, Nicola, additional, Pasanen, Markku, additional, Pfuhler, Stefan, additional, Phillips, Barry, additional, Sabbioni, Enrico, additional, Sanner, Tore, additional, and Vanparys, Philippe, additional
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- 2005
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22. 3.10. Carcinogenicity
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Maurici, Daniela, primary, Aardema, Marilyn, additional, Corvi, Raffaella, additional, Kleber, Marcus, additional, Krul, Cyrille, additional, Laurent, Christian, additional, Loprieno, Nicola, additional, Pasanen, Markku, additional, Pfuhler, Stefan, additional, Phillips, Barry, additional, Prentice, David, additional, Sabbioni, Enrico, additional, Sanner, Tore, additional, and Vanparys, Philippe, additional
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- 2005
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23. New insights into the mechanisms involved in renal proximal tubular damage induced in vitro by ochratoxin A
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Gennari, Alessandra, primary, Pazos, Patricia, additional, Boveri, Monica, additional, Callaghan, Robert, additional, Casado, Juan, additional, Maurici, Daniela, additional, Corsini, Emanuela, additional, and Prieto, Pilar, additional
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- 2004
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24. The Tumor Suppressor Gene TP53: Implications for Cancer Management and Therapy
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Seemann, Séverine, primary, Maurici, Daniela, additional, Olivier, Magali, additional, Fromentel, Claude Caron, additional, and Hainaut, Pierre, additional
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- 2004
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25. Restoration of wild-type conformation and activity of a temperature-sensitive mutant of p53 (p53V272M) by the cytoprotective aminothiol WR1065 in the esophageal cancer cell line TE-1
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North, Sophie, primary, Pluquet, Olivier, additional, Maurici, Daniela, additional, El Ghissassi, Fatiha, additional, and Hainaut, Pierre, additional
- Published
- 2002
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26. Molecular and Clinical Differences between Adenocarcinomas of the Esophagus and of the Gastric Cardia
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Tanière, Philippe, primary, Martel-Planche, Ghislaine, additional, Maurici, Daniela, additional, Lombard-Bohas, Catherine, additional, Scoazec, Jean-Yves, additional, Montesano, Ruggero, additional, Berger, Françoise, additional, and Hainaut, Pierre, additional
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- 2001
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27. Frequency and Implications of Chromosome 8 and 12 Gains in Ewing Sarcoma
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Maurici, Daniela, primary, Perez-Atayde, Antonio, additional, Grier, Holcombe E, additional, Baldini, Nicola, additional, Serra, Massimo, additional, and Fletcher, Jonathan A, additional
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- 1998
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28. Cytologic and fluorescence in situ hybridization (FISH) examination of metanephric adenoma
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Renshaw, Andrew A., primary, Maurici, Daniela, additional, and Fletcher, Jonathan A., additional
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- 1997
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29. Immunostaining of the p30/32MIC2 antigen and molecular detection of EWS rearrangements for the diagnosis of Ewing's sarcoma and peripheral neuroectodermal tumor
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Scotlandi, Katia, primary, Serra, Massimo, additional, Manara, Maria Cristina, additional, Benini, Stefania, additional, Sarti, Manuela, additional, Maurici, Daniela, additional, Lollini, Pier-Luigi, additional, Picci, Piero, additional, Bertoni, Franco, additional, and Baldini, Nicola, additional
- Published
- 1996
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30. Pre‐Treatment of human osteosarcoma cells with N‐methylformamide enhances P‐glycoprotein expression and resistance to doxorubicin
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Scotlandi, Katia, primary, Serra, Massimo, additional, Manara, Maria Cristina, additional, Lollini, Pier‐Luigi, additional, Maurici, Daniela, additional, Bufalo, Donatella Del, additional, and Baldini, Nicola, additional
- Published
- 1994
- Full Text
- View/download PDF
31. Restoration of wild-type conformation and activity of a temperature-sensitive mutant of p53 (p53V272M) by the cytoprotective aminothiol WR1065 in the esophageal cancer cell line TE-1.
- Author
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North, Sophie, Pluquet, Olivier, Maurici, Daniela, El Ghissassi, Fatiha, and Hainaut, Pierre
- Published
- 2002
- Full Text
- View/download PDF
32. Adriamycin binding assay: a valuable chemosensitivity test in human osteosarcoma.
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Baldini, Nicola, Scotlandi, Katia, Serra, Massimo, Kusuzaki, Katsuyuki, Shikita, Toshiharu, Manara, Maria, Maurici, Daniela, and Campanacci, Mario
- Abstract
The reliability of a simple method evaluating the pattern of subcellular binding of Adriamycin (Adriamycin binding assay, ABA) as an index of sensitivity was demonstrated in different primary cultures and in sensitive and resistant cell lines of human osteosarcoma. After exposure to Adriamycin (10 μg/ml for 30 min at 37°C), living sensitive cells showed selective intranuclear uptake of the drug, whereas in resistant cells no distinct subcellular distribution was observed. The binding pattern of Adriamycin in sensitive and in highly resistant cells was inversely related to the expression of P-glycoprotein. However, low levels of resistance in vitro, not detectable by increased levels of expression of P-glycoprotein, were revealed by ABA. The use of ABA in combination with the estimate of P-glycoprotein expression is recommended in clinical practice as an accurate means for predicting the sensitivity of osteosarcoma to Adriamycin. [ABSTRACT FROM AUTHOR]
- Published
- 1993
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33. Outcome of the public consultation on the draft statement on genotoxicity assessment of chemical mixtures.
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Carfì, Maria, Manini, Paola, Martino, Carla, Maurici, Daniela, Morte, Juan Parra, Rossi, Annamaria, Vettori, Maria Vittoria, and Schlatter, Josef
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SCIENTIFIC community - Abstract
The European Food Safety Authority (EFSA) carried out a public consultation to receive input from the scientific community and all interested parties on the genotoxicity assessment of chemical mixtures. The draft statement was prepared by a dedicated working group of the Scientific Committee and endorsed by the Scientific Committee for public consultation at its 89th plenary meeting of 28‐29 May 2018. The public consultation for this document was open from 26 June until 9 September 2018. EFSA received 73 comments from 16 interested parties. EFSA's Scientific Committee wishes to thank all stakeholders for their contributions. This report presents statistics on the comments received and provides a summarised description of how the comments were addressed in the finalisation of the document. The stakeholders valuable and detailed comments were taken into account by the Scientific Committee to prepare an updated version of the statement on genotoxicity assessment of mixtures. The statement was discussed and adopted at the Scientific Committee plenary meeting on 22 November 2018, and is published in the EFSA Journal. This publication is linked to the following EFSA Journal article: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2019.5519/full [ABSTRACT FROM AUTHOR]
- Published
- 2019
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34. Guidance on aneugenicity assessment.
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More SJ, Bampidis V, Bragard C, Halldorsson TI, Hernández-Jerez AF, Hougaard Bennekou S, Koutsoumanis K, Lambré C, Machera K, Naegeli H, Nielsen SS, Schlatter J, Schrenk D, Turck D, Younes M, Aquilina G, Bignami M, Bolognesi C, Crebelli R, Gürtler R, Marcon F, Nielsen E, Vleminckx C, Carfì M, Martino C, Maurici D, Parra Morte J, Rossi A, and Benford D
- Abstract
The EFSA Scientific Committee was asked to provide guidance on the most appropriate in vivo tests to follow up on positive in vitro results for aneugenicity, and on the approach to risk assessment for substances that are aneugenic but not clastogenic nor causing gene mutations. The Scientific Committee confirmed that the preferred approach is to perform an in vivo mammalian erythrocyte micronucleus test with a relevant route of administration. If this is positive, it demonstrates that the substance is aneugenic in vivo . A negative result with evidence that the bone marrow is exposed to the test substance supports a conclusion that aneugenic activity is not expressed in vivo . If there is no evidence of exposure to the bone marrow, a negative result is viewed as inconclusive and further studies are required. The liver micronucleus assay, even though not yet fully validated, can provide supporting information for substances that are aneugenic following metabolic activation. The gastrointestinal micronucleus test, conversely, to be further developed, may help to assess aneugenic potential at the initial site of contact for substances that are aneugenic in vitro without metabolic activation. Based on the evidence in relation to mechanisms of aneugenicity, the Scientific Committee concluded that, in principle, health-based guidance values can be established for substances that are aneugenic but not clastogenic nor causing gene mutations, provided that a comprehensive toxicological database is available. For situations in which the toxicological database is not sufficient to establish health-based guidance values, some approaches to risk assessment are proposed. The Scientific Committee recommends further development of the gastrointestinal micronucleus test, and research to improve the understanding of aneugenicity to support risk assessment., (© 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)
- Published
- 2021
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- View/download PDF
35. Scientific Opinion of the Scientific Panel on Plant Protection Products and their Residues (PPR Panel) on the genotoxic potential of triazine amine (metabolite common to several sulfonylurea active substances).
- Author
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Hernandez-Jerez AF, Adriaanse P, Aldrich A, Berny P, Coja T, Duquesne S, Gimsing AL, Marinovich M, Millet M, Pelkonen O, Pieper S, Tiktak A, Topping CJ, Tzoulaki I, Widenfalk A, Wolterink G, Benford D, Aquilina G, Bignami M, Bolognesi C, Crebelli R, Guertler R, Marcon F, Nielsen E, Schlatter JR, Vleminckx C, Maurici D, and Parra Morte JM
- Abstract
The Panel received a mandate from the European Commission to assess the genotoxic potential of triazine amine based on available information submitted by the applicants. Available information includes experimental genotoxicity data on triazine amine, Quantitative Structure-Activity Relationship (QSAR) analysis and read across with structurally similar compounds. Based on the overall weight of evidence, the Panel, in agreement with the cross-cutting Working Group Genotoxicity, concluded that there is no concern for the potential of triazine amine to induce gene mutations and clastogenicity; however, the potential to induce aneugenicity was not adequately investigated. For a conclusion, an in vitro micronucleus assay performed with triazine amine would be needed., (© 2020 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)
- Published
- 2020
- Full Text
- View/download PDF
36. Genotoxicity assessment of chemical mixtures.
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More S, Bampidis V, Benford D, Boesten J, Bragard C, Halldorsson T, Hernandez-Jerez A, Hougaard-Bennekou S, Koutsoumanis K, Naegeli H, Nielsen SS, Schrenk D, Silano V, Turck D, Younes M, Aquilina G, Crebelli R, Gürtler R, Hirsch-Ernst KI, Mosesso P, Nielsen E, Solecki R, Carfì M, Martino C, Maurici D, Parra Morte J, and Schlatter J
- Abstract
The EFSA Scientific Committee addressed in this document the peculiarities related to the genotoxicity assessment of chemical mixtures. The EFSA Scientific Committee suggests that first a mixture should be chemically characterised as far as possible. Although the characterisation of mixtures is relevant also for other toxicity aspects, it is particularly significant for the assessment of genotoxicity. If a mixture contains one or more chemical substances that are individually assessed to be genotoxic in vivo via a relevant route of administration, the mixture raises concern for genotoxicity. If a fully chemically defined mixture does not contain genotoxic chemical substances, the mixture is of no concern with respect to genotoxicity. If a mixture contains a fraction of chemical substances that have not been chemically identified, experimental testing of the unidentified fraction should be considered as the first option or, if this is not feasible, testing of the whole mixture should be undertaken. If testing of these fraction(s) or of the whole mixture in an adequately performed set of in vitro assays provides clearly negative results, the mixture does not raise concern for genotoxicity. If in vitro testing provides one or more positive results, an in vivo follow-up study should be considered. For negative results in the in vivo follow-up test(s), the possible limitations of in vivo testing should be weighed in an uncertainty analysis before reaching a conclusion of no concern with respect to genotoxicity. For positive results in the in vivo follow-up test(s), it can be concluded that the mixture does raise a concern about genotoxicity., (© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)
- Published
- 2018
- Full Text
- View/download PDF
37. Clarification of some aspects related to genotoxicity assessment.
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Hardy A, Benford D, Halldorsson T, Jeger M, Knutsen HK, More S, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Silano V, Solecki R, Turck D, Younes M, Aquilina G, Crebelli R, Gürtler R, Hirsch-Ernst KI, Mosesso P, Nielsen E, van Benthem J, Carfì M, Georgiadis N, Maurici D, Parra Morte J, and Schlatter J
- Abstract
The European Commission requested EFSA to provide advice on the following: (1) the suitability of the unscheduled DNA synthesis (UDS) in vivo assay to follow-up positive results in in vitro gene mutation tests; (2) the adequacy to demonstrate target tissue exposure in in vivo studies, particularly in the mammalian erythrocyte micronucleus test; (3) the use of data in a weight-of-evidence approach to conclude on the genotoxic potential of substances and the consequent setting of health-based guidance values. The Scientific Committee concluded that the first question should be addressed in both a retrospective and a prospective way: for future assessments, it is recommended no longer performing the UDS test. For re-assessments, if the outcome of the UDS is negative, the reliability and significance of results should be carefully evaluated in a weight-of-evidence approach, before deciding whether more sensitive tests such as transgenic assay or in vivo comet assay would be needed to complete the assessment. Regarding the second question, the Scientific Committee concluded that it should be addressed in lines of evidence of bone marrow exposure: toxicity to the bone marrow in itself provides sufficient evidence to allow concluding on the validity of a negative outcome of a study. All other lines of evidence of target tissue exposure should be assessed within a weight-of-evidence approach. Regarding the third question, the Scientific Committee concluded that any available data that may assist in reducing the uncertainty in the assessment of the genotoxic potential of a substance should be taken into consideration. If the overall evaluation leaves no concerns for genotoxicity, health-based guidance values may be established. However, if concerns for genotoxicity remain, establishing health-based guidance values is not considered appropriate., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)
- Published
- 2017
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38. Scientific motivations and criteria to consider updating EFSA scientific assessments.
- Author
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Hardy A, Benford D, Halldorsson T, Jeger MJ, Knutsen KH, More S, Mortensen A, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V, Solecki R, Turck D, Brock T, Chesson A, Karenlampi S, Lambre C, Sanz Y, Goumperis T, Kleiner J, and Maurici D
- Abstract
EFSA is committed to assess and communicate the risks occurring in the food and feed chain from farm to fork and to provide other forms of scientific advice. This work, carried out by EFSA since its inception, has resulted in the adoption of thousands of scientific assessments. EFSA is obliged to re-assess past assessments in specific regulatory contexts such as those on food and feed additives, active substances in plant protection products and genetically modified food and feed. In other sectors, the consideration for updating past EFSA scientific assessments is taken on an ad hoc basis mainly depending on specific requests by risk managers or on EFSA self-tasking. If safety is potentially at stake in any area within EFSA's remit, the readiness to update past scientific assessments is important to keep EFSA at the forefront of science and to promote an effective risk assessment. Although this task might be very complex and resource demanding, it is fundamental to EFSA's mission. The present EFSA Scientific Committee opinion deals with scientific motivations and criteria to contribute to the timely updating of EFSA scientific assessments. It is recognised that the decision for updating should be agreed following careful consideration of all the relevant elements by the EFSA management, in collaboration with risk managers and stakeholders. The present opinion addresses the scientific approaches through which it would be possible for EFSA to increase the speed and effectiveness of the acquisition of new data, as well as, to improve the consequent evaluations to assess the relevance and reliability of new data in the context of contributing to the better definition of whether to update past scientific assessments., (© 2017 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.)
- Published
- 2017
- Full Text
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39. Genotoxicty and mutagenicity.
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Maurici D, Aardema M, Corvi R, Kleber M, Krul C, Laurent C, Loprieno N, Pasanen M, Pfuhler S, Phillips B, Sabbioni E, Sanner T, and Vanparys P
- Subjects
- Animal Testing Alternatives legislation & jurisprudence, Animal Testing Alternatives standards, Animals, Carcinogenicity Tests methods, Carcinogens chemistry, Carcinogens classification, Cells, Cultured, Consumer Product Safety legislation & jurisprudence, Consumer Product Safety standards, Cosmetics chemistry, Cosmetics classification, European Union, Humans, Mutagenicity Tests methods, Mutagens chemistry, Mutagens classification, Structure-Activity Relationship, Carcinogens toxicity, Cosmetics toxicity, Mutagens toxicity
- Published
- 2005
- Full Text
- View/download PDF
40. Carcinogenicity.
- Author
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Maurici D, Aardema M, Corvi R, Kleber M, Krul C, Laurent C, Loprieno N, Pasanen M, Pfuhler S, Phillips B, Prentice D, Sabbioni E, Sanner T, and Vanparys P
- Subjects
- Animal Testing Alternatives legislation & jurisprudence, Animal Testing Alternatives standards, Animals, Carcinogenicity Tests methods, Carcinogens chemistry, Carcinogens classification, Cell Transformation, Neoplastic drug effects, Cell Transformation, Neoplastic pathology, Cells, Cultured, Consumer Product Safety legislation & jurisprudence, Consumer Product Safety standards, Cosmetics chemistry, Cosmetics classification, European Union, Gap Junctions drug effects, Gap Junctions pathology, Mice, Mice, Transgenic, Quantitative Structure-Activity Relationship, Rats, Carcinogens toxicity, Cosmetics toxicity
- Published
- 2005
- Full Text
- View/download PDF
41. Initiation of human astrocytoma by clonal evolution of cells with progressive loss of p53 functions in a patient with a 283H TP53 germ-line mutation: evidence for a precursor lesion.
- Author
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Fulci G, Ishii N, Maurici D, Gernert KM, Hainaut P, Kaur B, and Van Meir EG
- Subjects
- Adult, Cell Division genetics, Cell Transformation, Neoplastic genetics, Cyclin-Dependent Kinase Inhibitor p21, Cyclins genetics, DNA, Neoplasm genetics, DNA, Neoplasm metabolism, Disease Progression, Gene Expression Regulation, Neoplastic, Humans, Male, Models, Molecular, Neoplasm Recurrence, Local genetics, Proto-Oncogene Proteins genetics, Transcriptional Activation, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, bcl-2-Associated X Protein, Astrocytoma genetics, Brain Neoplasms genetics, Genes, p53 genetics, Germ-Line Mutation, Point Mutation, Precancerous Conditions genetics, Proto-Oncogene Proteins c-bcl-2, Tumor Suppressor Protein p53 physiology
- Abstract
Little is known about the genetic and molecular events leading to the early stages of human astrocytoma formation. To examine this issue, we analyzed the significance of sequential accumulation of two somatic point mutations (R267W and E258D) in the TP53 gene during the initiation of astrocytoma in a patient born with a single germ-line p53 point mutation (R283H). We adapted a p53 transcriptional assay in yeast to establish the temporal occurrence and allelic distribution of the p53 mutations present in the patient and characterized these mutations through functional assays and structural modeling. Our results show that the first somatic mutation occurred at codon 267 on the p53 allele harboring the germ-line mutation R283H, whereas the second somatic mutation occurred in the remaining wild-type (wt) allele at codon 258. These two mutations induced the formation of tumor cells with the genotype p53(267W+283H/258D), which comprised 70% of the cells in the primary WHO grade II astrocytoma. Another 8% of cells within the tumor had the partially mutated genotype p53(267W+283H/WT) and represented the remnants of a clinically undetectable intermediate stage of astrocytic neoplastic transformation. The remaining 22% of cells had the constitutive p53(283H/WT) genotype and likely consisted of nontumor cells. Functional analysis of the p53 alleles present in the patient's tumor indicated that the germ-line p53(R283H) could transactivate the CDKN1A((p21, WAF1, cip1, SDI1)) but not the BAX gene and retained the ability to induce growth arrest of human glioblastoma cells. The p53(R267W+R283H) and p53(E258D) were incapable of transactivating either promoter or inducing growth arrest. Modeling of p53 interaction with DNA suggests that R283H mutation may weaken the sequence-specific interaction of p53 lysine 120 with the BAX gene but not the CDKN1A p53-responsive elements. Taken together, these results have characterized, for the first time, the genetic events defining a clinically undetectable precursor lesion leading to a grade II astrocytoma. They also suggest that astrocytoma initiation in this patient resulted from monoclonal evolution driven by a sequential loss of proapoptotic and growth arrest functions of p53.
- Published
- 2002
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