Oxidative Stress, Mutations and Chromosomal Aberrations Induced by In Vitro and In Vivo Exposure to Furan
Furan is a volatile compound that is formed in foods during thermal processing. It is classified as a possible human carcinogen by international authorities based on sufficient evidence of carcinogenicity from studies in experimental animals. Although a vast number of studies both in vitro and in vi...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9687 |
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| author | Maria Teresa Russo Gabriele De Luca Nieves Palma Paola Leopardi Paolo Degan Serena Cinelli Gaetano Pepe Pasquale Mosesso Emma Di Carlo Carlo Sorrentino Piero Musiani Riccardo Crebelli Margherita Bignami Eugenia Dogliotti |
| author_facet | Maria Teresa Russo Gabriele De Luca Nieves Palma Paola Leopardi Paolo Degan Serena Cinelli Gaetano Pepe Pasquale Mosesso Emma Di Carlo Carlo Sorrentino Piero Musiani Riccardo Crebelli Margherita Bignami Eugenia Dogliotti |
| author_sort | Maria Teresa Russo |
| collection | DOAJ |
| description | Furan is a volatile compound that is formed in foods during thermal processing. It is classified as a possible human carcinogen by international authorities based on sufficient evidence of carcinogenicity from studies in experimental animals. Although a vast number of studies both in vitro and in vivo have been performed to investigate furan genotoxicity, the results are inconsistent, and its carcinogenic mode of action remains to be clarified. Here, we address the mutagenic and clastogenic activity of furan and its prime reactive metabolite cis-2 butene-1,4-dial (BDA) in mammalian cells in culture and in mouse animal models in a search for DNA lesions responsible of these effects. To this aim, Fanconi anemia-derived human cell lines defective in the repair of DNA inter-strand crosslinks (ICLs) and <i>Ogg1</i><sup>−/−</sup> mice defective in the removal of 8-hydroxyguanine from DNA, were used. We show that both furan and BDA present a weak (if any) mutagenic activity but are clear inducers of clastogenic damage. ICLs are strongly indicated as key lesions for chromosomal damage whereas oxidized base lesions are unlikely to play a critical role. |
| first_indexed | 2024-03-10T07:36:58Z |
| format | Article |
| id | doaj.art-a457239ee2ba4c4caa1d09b4d80ad950 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:36:58Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a457239ee2ba4c4caa1d09b4d80ad9502023-11-22T13:25:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218968710.3390/ijms22189687Oxidative Stress, Mutations and Chromosomal Aberrations Induced by In Vitro and In Vivo Exposure to FuranMaria Teresa Russo0Gabriele De Luca1Nieves Palma2Paola Leopardi3Paolo Degan4Serena Cinelli5Gaetano Pepe6Pasquale Mosesso7Emma Di Carlo8Carlo Sorrentino9Piero Musiani10Riccardo Crebelli11Margherita Bignami12Eugenia Dogliotti13National Centre for Chemical Products, Cosmetics and Consumer Protection, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyOncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyIRCCS AOU San Martino, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genoa, ItalyEuropean Research Biology Center, Via Tito Speri 12/14, Pomezia, 00071 Rome, ItalyDipartimento di Scienze Ecologiche e Biologiche, Università degli Studi della Tuscia, 01100 Viterbo, ItalyDipartimento di Scienze Ecologiche e Biologiche, Università degli Studi della Tuscia, 01100 Viterbo, ItalyDepartment of Medicine and Sciences of Aging, “G. d’Annunzio” University of Chieti-Pescara, 66022 Chieti, ItalyDepartment of Medicine and Sciences of Aging, “G. d’Annunzio” University of Chieti-Pescara, 66022 Chieti, ItalyDepartment of Medicine and Sciences of Aging, “G. d’Annunzio” University of Chieti-Pescara, 66022 Chieti, ItalyDepartment of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyFuran is a volatile compound that is formed in foods during thermal processing. It is classified as a possible human carcinogen by international authorities based on sufficient evidence of carcinogenicity from studies in experimental animals. Although a vast number of studies both in vitro and in vivo have been performed to investigate furan genotoxicity, the results are inconsistent, and its carcinogenic mode of action remains to be clarified. Here, we address the mutagenic and clastogenic activity of furan and its prime reactive metabolite cis-2 butene-1,4-dial (BDA) in mammalian cells in culture and in mouse animal models in a search for DNA lesions responsible of these effects. To this aim, Fanconi anemia-derived human cell lines defective in the repair of DNA inter-strand crosslinks (ICLs) and <i>Ogg1</i><sup>−/−</sup> mice defective in the removal of 8-hydroxyguanine from DNA, were used. We show that both furan and BDA present a weak (if any) mutagenic activity but are clear inducers of clastogenic damage. ICLs are strongly indicated as key lesions for chromosomal damage whereas oxidized base lesions are unlikely to play a critical role.https://www.mdpi.com/1422-0067/22/18/9687furanmutagenicityclastogenicityoxidative DNA base damageinter-strand cross-links |
| spellingShingle | Maria Teresa Russo Gabriele De Luca Nieves Palma Paola Leopardi Paolo Degan Serena Cinelli Gaetano Pepe Pasquale Mosesso Emma Di Carlo Carlo Sorrentino Piero Musiani Riccardo Crebelli Margherita Bignami Eugenia Dogliotti Oxidative Stress, Mutations and Chromosomal Aberrations Induced by In Vitro and In Vivo Exposure to Furan International Journal of Molecular Sciences furan mutagenicity clastogenicity oxidative DNA base damage inter-strand cross-links |
| title | Oxidative Stress, Mutations and Chromosomal Aberrations Induced by In Vitro and In Vivo Exposure to Furan |
| title_full | Oxidative Stress, Mutations and Chromosomal Aberrations Induced by In Vitro and In Vivo Exposure to Furan |
| title_fullStr | Oxidative Stress, Mutations and Chromosomal Aberrations Induced by In Vitro and In Vivo Exposure to Furan |
| title_full_unstemmed | Oxidative Stress, Mutations and Chromosomal Aberrations Induced by In Vitro and In Vivo Exposure to Furan |
| title_short | Oxidative Stress, Mutations and Chromosomal Aberrations Induced by In Vitro and In Vivo Exposure to Furan |
| title_sort | oxidative stress mutations and chromosomal aberrations induced by in vitro and in vivo exposure to furan |
| topic | furan mutagenicity clastogenicity oxidative DNA base damage inter-strand cross-links |
| url | https://www.mdpi.com/1422-0067/22/18/9687 |
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