BioProject

Titanium dioxide (TiO2) is present in many different food products as food additive E171 and is currently scrutinized, due to its potential adverse effects, including the stimulation of tumor formation in the gastrointestinal tract. More...

Titanium dioxide (TiO2) is present in many different food products as food additive E171 and 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. In phase I of this study, tumor formation was studied following the exposure to 5 mg/kgbw/day of E171 for 9 weeks. E171-exposure increased the number of transgenic mice with colorectal tumors as well as the average number and size of these tumors. Colorectal adenocarcinomas were accompanied by enhanced hyperplasia in epithelial cells and lymphatic nodules at the base of the polyps. In phase II, gene expression changes in the colon were analyzed after exposure to 1, 2, and 5 mg/kgbw/day of E171 for 2, 7, 14, and 21 days. 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. Overall design: Total of 99 samples. Per time point (2, 7, 14, and 21 days) and dose (1, 2, and 5 mg/kg:bw/day) there was 3 female and 4 male mice assigned, which were exposed to E171 via intragastric gavage. Dose was administered 5 days a week, Mo-Fr. Less...