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
Por:
Bischoff, Nicolaj S., Proquin, Heloise, Jetten, Marlon J., Schrooders, Yannick, Jonkhout M.C.M., Briede, Jacco J., van Breda, Simone G., Jennen D.G.J., Medina-Reyes, I, Estefany, Delgado-Buenrostro, Norma L., Chirino, I, Yolanda, van Loveren, Henk, de Kok, Theo M.
Publicada:
1 abr 2022
Resumen:
Titanium dioxide (TiO2) 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 Apc-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, lymphatic nodules at the base of the
polyps, and increased tumor size. In the main study, tumor formation was
studied following the exposure to 5 mg/kg(bw)/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(bw)/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.
Filiaciones:
Bischoff, Nicolaj S.:
Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, 6229 ER, Netherlands
Proquin, Heloise:
Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, 6229 ER, Netherlands
National Institute for Public Health and Environment (RIVM), Bilthoven, 3721 MA, Netherlands
Jetten, Marlon J.:
Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, 6229 ER, Netherlands
Faculty of Health, Medicine and Life Science, Maastricht University Medical Center, Maastricht, 6229 ES, Netherlands
Schrooders, Yannick:
Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, 6229 ER, Netherlands
Laboratory of Biosignaling & Therapeutics, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, 3000, Belgium
Jonkhout M.C.M.:
Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, 6229 ER, Netherlands
Laboratory of Biosignaling & Therapeutics, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, 3000, Belgium
Briede, Jacco J.:
Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, 6229 ER, Netherlands
van Breda, Simone G.:
Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, 6229 ER, Netherlands
Jennen D.G.J.:
Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, 6229 ER, Netherlands
Medina-Reyes, I, Estefany:
Laboratorio de Carcinogénesis y Toxicología, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City, 54090, Mexico
Delgado-Buenrostro, Norma L.:
Laboratorio de Carcinogénesis y Toxicología, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City, 54090, Mexico
Chirino, I, Yolanda:
Laboratorio de Carcinogénesis y Toxicología, Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City, 54090, Mexico
van Loveren, Henk:
Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, 6229 ER, Netherlands
de Kok, Theo M.:
Department of Toxicogenomics, GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, 6229 ER, Netherlands
Green Published, gold, Gold
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