Prioritization of Mycotoxins Based on Their Genotoxic Potential with an In Silico-In Vitro Strategy
Humans are widely exposed to a great variety of mycotoxins and their mixtures. Therefore, it is important to design strategies that allow prioritizing mycotoxins based on their toxic potential in a time and cost-effective manner. A strategy combining in silico tools (Phase 1), including an expert kn...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/10/734 |
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| author | Maria Alonso-Jauregui María Font Elena González-Peñas Adela López de Cerain Ariane Vettorazzi |
| author_facet | Maria Alonso-Jauregui María Font Elena González-Peñas Adela López de Cerain Ariane Vettorazzi |
| author_sort | Maria Alonso-Jauregui |
| collection | DOAJ |
| description | Humans are widely exposed to a great variety of mycotoxins and their mixtures. Therefore, it is important to design strategies that allow prioritizing mycotoxins based on their toxic potential in a time and cost-effective manner. A strategy combining in silico tools (Phase 1), including an expert knowledge-based (DEREK Nexus<sup>®</sup><sub>,</sub> Lhasa Limited, Leeds, UK) and a statistical-based platform (VEGA QSAR©, Mario Negri Institute, Milan, Italy), followed by the in vitro SOS/umu test (Phase 2), was applied to a set of 12 mycotoxins clustered according to their structure into three groups. Phase 1 allowed us to clearly classify group 1 (aflatoxin and sterigmatocystin) as mutagenic and group 3 (ochratoxin A, zearalenone and fumonisin B1) as non-mutagenic. For group 2 (trichothecenes), contradictory conclusions were obtained between the two in silico tools, being out of the applicability domain of many models. Phase 2 confirmed the results obtained in the previous phase for groups 1 and 3. It also provided extra information regarding the role of metabolic activation in aflatoxin B1 and sterigmatocystin mutagenicity. Regarding group 2, equivocal results were obtained in few experiments; however, the group was finally classified as non-mutagenic. The strategy used correlated with the published Ames tests, which detect point mutations. Few alerts for chromosome aberrations could be detected. The SOS/umu test appeared as a good screening test for mutagenicity that can be used in the absence and presence of metabolic activation and independently of Phase 1, although the in silico–in vitro combination gave more information for decision making. |
| first_indexed | 2024-03-10T06:09:35Z |
| format | Article |
| id | doaj.art-8cb6fd86974a4915befdd57e0cb32207 |
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| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T06:09:35Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-8cb6fd86974a4915befdd57e0cb322072023-11-22T20:13:38ZengMDPI AGToxins2072-66512021-10-01131073410.3390/toxins13100734Prioritization of Mycotoxins Based on Their Genotoxic Potential with an In Silico-In Vitro StrategyMaria Alonso-Jauregui0María Font1Elena González-Peñas2Adela López de Cerain3Ariane Vettorazzi4Department of Pharmacology and Toxicology, Research Group MITOX, School of Pharmacy and Nutrition, Universidad de Navarra, 31008 Pamplona, SpainDepartment of Pharmaceutical Technology and Chemistry, Research Group MITOX, School of Pharmacy and Nutrition, Universidad de Navarra, 31008 Pamplona, SpainDepartment of Pharmaceutical Technology and Chemistry, Research Group MITOX, School of Pharmacy and Nutrition, Universidad de Navarra, 31008 Pamplona, SpainDepartment of Pharmacology and Toxicology, Research Group MITOX, School of Pharmacy and Nutrition, Universidad de Navarra, 31008 Pamplona, SpainDepartment of Pharmacology and Toxicology, Research Group MITOX, School of Pharmacy and Nutrition, Universidad de Navarra, 31008 Pamplona, SpainHumans are widely exposed to a great variety of mycotoxins and their mixtures. Therefore, it is important to design strategies that allow prioritizing mycotoxins based on their toxic potential in a time and cost-effective manner. A strategy combining in silico tools (Phase 1), including an expert knowledge-based (DEREK Nexus<sup>®</sup><sub>,</sub> Lhasa Limited, Leeds, UK) and a statistical-based platform (VEGA QSAR©, Mario Negri Institute, Milan, Italy), followed by the in vitro SOS/umu test (Phase 2), was applied to a set of 12 mycotoxins clustered according to their structure into three groups. Phase 1 allowed us to clearly classify group 1 (aflatoxin and sterigmatocystin) as mutagenic and group 3 (ochratoxin A, zearalenone and fumonisin B1) as non-mutagenic. For group 2 (trichothecenes), contradictory conclusions were obtained between the two in silico tools, being out of the applicability domain of many models. Phase 2 confirmed the results obtained in the previous phase for groups 1 and 3. It also provided extra information regarding the role of metabolic activation in aflatoxin B1 and sterigmatocystin mutagenicity. Regarding group 2, equivocal results were obtained in few experiments; however, the group was finally classified as non-mutagenic. The strategy used correlated with the published Ames tests, which detect point mutations. Few alerts for chromosome aberrations could be detected. The SOS/umu test appeared as a good screening test for mutagenicity that can be used in the absence and presence of metabolic activation and independently of Phase 1, although the in silico–in vitro combination gave more information for decision making.https://www.mdpi.com/2072-6651/13/10/734mycotoxinsin silicoSOS/umu testgenotoxicityprioritization |
| spellingShingle | Maria Alonso-Jauregui María Font Elena González-Peñas Adela López de Cerain Ariane Vettorazzi Prioritization of Mycotoxins Based on Their Genotoxic Potential with an In Silico-In Vitro Strategy Toxins mycotoxins in silico SOS/umu test genotoxicity prioritization |
| title | Prioritization of Mycotoxins Based on Their Genotoxic Potential with an In Silico-In Vitro Strategy |
| title_full | Prioritization of Mycotoxins Based on Their Genotoxic Potential with an In Silico-In Vitro Strategy |
| title_fullStr | Prioritization of Mycotoxins Based on Their Genotoxic Potential with an In Silico-In Vitro Strategy |
| title_full_unstemmed | Prioritization of Mycotoxins Based on Their Genotoxic Potential with an In Silico-In Vitro Strategy |
| title_short | Prioritization of Mycotoxins Based on Their Genotoxic Potential with an In Silico-In Vitro Strategy |
| title_sort | prioritization of mycotoxins based on their genotoxic potential with an in silico in vitro strategy |
| topic | mycotoxins in silico SOS/umu test genotoxicity prioritization |
| url | https://www.mdpi.com/2072-6651/13/10/734 |
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