The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer
Titanium dioxide (TiO<sub>2</sub>) is present in many different food products as the food additive E171, which is currently scrutinized due to its potential adverse effects, including the stimulation of tumor formation in the gastrointestinal tract. We developed a transgenic mouse model...
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| Materialtyp: | Artikel |
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MDPI AG
2022-04-01
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| Serie: | Nanomaterials |
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| Länkar: | https://www.mdpi.com/2079-4991/12/8/1256 |
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| author | Nicolaj S. Bischoff Héloïse Proquin Marlon J. Jetten Yannick Schrooders Marloes C. M. Jonkhout Jacco J. Briedé Simone G. van Breda Danyel G. J. Jennen Estefany I. Medina-Reyes Norma L. Delgado-Buenrostro Yolanda I. Chirino Henk van Loveren Theo M. de Kok |
| author_facet | Nicolaj S. Bischoff Héloïse Proquin Marlon J. Jetten Yannick Schrooders Marloes C. M. Jonkhout Jacco J. Briedé Simone G. van Breda Danyel G. J. Jennen Estefany I. Medina-Reyes Norma L. Delgado-Buenrostro Yolanda I. Chirino Henk van Loveren Theo M. de Kok |
| author_sort | Nicolaj S. Bischoff |
| collection | DOAJ |
| description | Titanium dioxide (TiO<sub>2</sub>) is present in many different food products as the food additive E171, which is currently scrutinized due to its potential adverse effects, including the stimulation of tumor formation in the gastrointestinal tract. We developed a transgenic mouse model to examine the effects of E171 on colorectal cancer (CRC), using the Cre-LoxP system to create an <i>Apc</i>-gene-knockout model which spontaneously develops colorectal tumors. A pilot study showed that E171 exposed mice developed colorectal adenocarcinomas, which were accompanied by enhanced hyperplasia in epithelial cells, and increased tumor size. In the main study, tumor formation was studied following the exposure to 5 mg/kg<sub>bw</sub>/day of E171 for 9 weeks (Phase I). E171 exposure showed a statistically nonsignificant increase in the number of colorectal tumors in these transgenic mice, as well as a statistically nonsignificant increase in the average number of mice with tumors. Gene expression changes in the colon were analyzed after exposure to 1, 2, and 5 mg/kg<sub>bw</sub>/day of E171 for 2, 7, 14, and 21 days (Phase II). Whole-genome mRNA analysis revealed the modulation of genes in pathways involved in the regulation of gene expression, cell cycle, post-translational modification, nuclear receptor signaling, and circadian rhythm. The processes associated with these genes might be involved in the enhanced tumor formation and suggest that E171 may contribute to tumor formation and progression by modulation of events related to inflammation, activation of immune responses, cell cycle, and cancer signaling. |
| first_indexed | 2024-03-11T10:52:14Z |
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| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-11T10:52:14Z |
| publishDate | 2022-04-01 |
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| series | Nanomaterials |
| spelling | doaj.art-8e4a4d9481344b9a9b9922d9f6f427722023-11-13T15:07:22ZengMDPI AGNanomaterials2079-49912022-04-01128125610.3390/nano12081256The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal CancerNicolaj S. Bischoff0Héloïse Proquin1Marlon J. Jetten2Yannick Schrooders3Marloes C. M. Jonkhout4Jacco J. Briedé5Simone G. van Breda6Danyel G. J. Jennen7Estefany I. Medina-Reyes8Norma L. Delgado-Buenrostro9Yolanda I. Chirino10Henk van Loveren11Theo M. de Kok12Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 ER Maastricht, The NetherlandsDepartment of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 ER Maastricht, The NetherlandsDepartment of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 ER Maastricht, The NetherlandsDepartment of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 ER Maastricht, The NetherlandsDepartment of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 ER Maastricht, The NetherlandsDepartment of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 ER Maastricht, The NetherlandsDepartment of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 ER Maastricht, The NetherlandsDepartment of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 ER Maastricht, The NetherlandsLaboratorio de Carcinogénesis y Toxicología, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City 54090, MexicoLaboratorio de Carcinogénesis y Toxicología, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City 54090, MexicoLaboratorio de Carcinogénesis y Toxicología, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City 54090, MexicoDepartment of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 ER Maastricht, The NetherlandsDepartment of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, 6229 ER Maastricht, The NetherlandsTitanium dioxide (TiO<sub>2</sub>) is present in many different food products as the food additive E171, which is currently scrutinized due to its potential adverse effects, including the stimulation of tumor formation in the gastrointestinal tract. We developed a transgenic mouse model to examine the effects of E171 on colorectal cancer (CRC), using the Cre-LoxP system to create an <i>Apc</i>-gene-knockout model which spontaneously develops colorectal tumors. A pilot study showed that E171 exposed mice developed colorectal adenocarcinomas, which were accompanied by enhanced hyperplasia in epithelial cells, and increased tumor size. In the main study, tumor formation was studied following the exposure to 5 mg/kg<sub>bw</sub>/day of E171 for 9 weeks (Phase I). E171 exposure showed a statistically nonsignificant increase in the number of colorectal tumors in these transgenic mice, as well as a statistically nonsignificant increase in the average number of mice with tumors. Gene expression changes in the colon were analyzed after exposure to 1, 2, and 5 mg/kg<sub>bw</sub>/day of E171 for 2, 7, 14, and 21 days (Phase II). Whole-genome mRNA analysis revealed the modulation of genes in pathways involved in the regulation of gene expression, cell cycle, post-translational modification, nuclear receptor signaling, and circadian rhythm. The processes associated with these genes might be involved in the enhanced tumor formation and suggest that E171 may contribute to tumor formation and progression by modulation of events related to inflammation, activation of immune responses, cell cycle, and cancer signaling.https://www.mdpi.com/2079-4991/12/8/1256titanium dioxideE171micetransgenictumor formationgene expression |
| spellingShingle | Nicolaj S. Bischoff Héloïse Proquin Marlon J. Jetten Yannick Schrooders Marloes C. M. Jonkhout Jacco J. Briedé Simone G. van Breda Danyel G. J. Jennen Estefany I. Medina-Reyes Norma L. Delgado-Buenrostro Yolanda I. Chirino Henk van Loveren Theo M. de Kok The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer Nanomaterials titanium dioxide E171 mice transgenic tumor formation gene expression |
| title | The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer |
| title_full | The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer |
| title_fullStr | The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer |
| title_full_unstemmed | The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer |
| title_short | The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer |
| title_sort | effects of the food additive titanium dioxide e171 on tumor formation and gene expression in the colon of a transgenic mouse model for colorectal cancer |
| topic | titanium dioxide E171 mice transgenic tumor formation gene expression |
| url | https://www.mdpi.com/2079-4991/12/8/1256 |
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