Transcriptomics effects of ingestion of food additive titanium dioxide (E171) in the colon of a chemically induced colorectal cancer model
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PROVIDER: PRJNA431295 | ENA |
REPOSITORIES: ENA
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Project description:Exposure to titanium dioxide (TiO2) food additive by ingestion increased over the years. TiO2 is used in food to give a brighter, fresher colour to sweets, cookies, salad dressing under the name E171. New studies on E171 showed that after ingestion in a colorectal cancer mouse model, a significant increased number of colorectal tumours were found. In addition, short-term exposure to E171 induces gene expression changes in relation to oxidative stress responses, an impairment of the immune system, activation of signalling and cancer-related genes. Furthermore, dysregulation of the immune system was also observed after ingestion of E171 in rats. E171 comprises nanoparticles (NPs) and microparticles (MPs). Previous in vitro studies showed the capacity of E171, TiO2 NPs and MPs to induce oxidative stress, DNA damage, and induction of the micronuclei. The aim of our study was to investigate the relative contribution of the NPs and MPs fractions to the effects of E171 at the molecular level. This investigation was performed using in vitro exposure of Caco-2 cells to E171 as well as the NPs and MPs fractions of TiO2 and assessing effects with genome wide gene expression analysis. Results showed that the E171, TiO2 NPs and MPs induce gene expression changes in signalling, inflammation, immune system, transport, and cancer. Contribution of NPs was observed on genes involved in TLR cascade, MHC class I and II presentation, late cornified envelope, potassium channels, and cell cycle. MPs contribution was observed with changes in gene expression on a target to Hedgehog family, α-defensins, cadherin and cholinergic receptors. The gene expression changes associated with the immune system and inflammation induced by E171, MPs, and NPs suggest the creation of a favourable environment for cancer development.
2019-11-22 | GSE110410 | GEO
Project description:Colorectal cancer is one of the most common cancers worldwide. Factors that could influence the increase or reduction of the risks, including dietary pattern, are under investigation. Previous studies showed the capacity of food additive titanium dioxide (E171) to induce DNA damage in vitro and facilitate growth of colorectal tumors in vivo. The aim of this study is to understand the molecular mechanisms behind these effects of E171 exposure. BALB/c mice were exposed by gavage to 5 mg/kgbw/day of E171 for 2, 7, 14 and 21 days. Transcriptome changes of the response to E171 exposure were studied by whole genome mRNA microarray analysis on the distal colons of the mice. The results showed significant changes in the transcriptome, mainly gene expression changes of the olfactory/GPCR receptor family, oxidative stress, immune responses and of cancer related genes. These pathways may represent the underlying molecular mechanisms by which E171 facilitates tumor formation in the colon of these mice.
2018-01-24 | GSE92563 | GEO
Project description:Titanium dioxide, a white colorant, is the mineral the most produced worldwide. It is used in food under the name of E171. Previous studies showed that in a chemically induced colorectal cancer mouse model, E171 increase significantly the number of tumours. The aim of this study was to understand the molecular mechanisms behind these effects of E171 exposure. BALB/c mice were exposed by gavage to 5 mg/kg bw/day of E171 for 2, 7, 14 and 21 days. Whole genome mRNA microarray analyses on the distal colon were performed. The results show that E171 induced a downregulation of genes involved in the innate and adaptive immune system, suggesting impairment of this system. In addition, over time, signalling genes involved in colorectal cancer and other types of cancers were modulated. In relation to cancer development, effects potentially associated with oxidative stress were observed through modulation of genes related to antioxidant production. E171 affected genes involved in biotransformation of xenobiotics which can form reactive intermediates resulting in toxicological effects. These transcriptomics data reflect the early biological responses induced by E171 which precede tumour formation in an AOM/DSS mouse model.
2018-07-15 | GSE109520 | GEO
Project description:Microarrays after exposure in Caco-2 cells to titanium dioxide food additive E171 and titanium dioxide nanoparticles and microparticles
| PRJNA433654 | ENA
Project description:Interventions: This study is a cross-over design, including only healthy volunteers. A cross-over design was chosen because it is the most appropriate design for this study: it will reduce the individual differences by allowing every subject to be his own control.
This study will be done in 4 weeks and include 2 periods. The volunteers will be randomized in two groups: one group will start with the intervention period and the other one will start with the control period. After, these 2 weeks of intervention or control periods, the volunteers will start the control period and intervention period respectively for another 2 weeks.
The time of exposure is 2 weeks. Indeed, it takes 5 to 7 days for the turnover of the epithelial cells in the gut. This will ensure the exposure of all the cells of the luminal surface of the colon.
The control period, is meant to reduce to a minimum the ingestion of E171 in order to have all the volunteers to start the same level of E171. During this period the volunteers will receive a list of products to avoid like cookies, chewing gum, certain toothpaste that are known to contain a significant amount of E171.
The intervention period, is meant to control the amount of E171 that the volunteers will ingest. A concentration, 0.82 mg/kg bw/day, corresponding to a normal daily consumption will be given to the volunteers. The quantity will be adjusted to the body weight and dispersed in yoghurt that will be eaten at breakfast, lunch and dinner.
In order to verify the compliance of the subjects, once in every period the subjects will prepare a package that include exactly what they ate and drank all day. This food package will be mixed and tested for TiO2 content.
Primary outcome(s): The primary outcome parameters are differences in transcriptomic markers after consumption of food additive E171. These outcomes in humans will shed light on the relevance of markers identified in preclinical studies, and how the animal data on the risk of facilitation of tumour growth can be extrapolated to humans
Study Design: Randomized controlled trial, Single blinded (masking used), N/A , unknown, Crossover
| 20119 | ecrin-mdr-crc
Project description:Titanium dioxide nanofiber (TDNF) is widely used in the manufacture of various household products including cosmetics. As a result, there is a possibility of negative impact on human health. The goal of the present study is to investigate the short-term effects of titanium dioxide nanofiber ingestion of male Sprague Dawley rats. TDNF was fabricated via electrospinning method, followed by dissolution in water. Six- to seven-week-old male Sprague Dawley rats were exposed to a total of 0, 40, and 60 ppm of TDNF for 2 weeks via oral gavage. Lungs and other tissues were autopsied and excised immediately frozen in liquid nitrogen and stored at -80 deg C until analysis. Total RNA was converted to single-stranded sense-target, fragmented, labeled, and hybridized to the Affymetrix Rat Gene ST 2.0 microarray according to the manufacturer’s protocol.
2023-08-31 | E-MTAB-13260 | biostudies-arrayexpress
Project description:The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E 171) based on new relevant scientific evidence considered by the Panel to be reliable, including data obtained with TiO2 nanoparticles (NPs) and data from an extended one-generation reproductive toxicity (EOGRT) study. Less than 50% of constituent particles by number in E 171 have a minimum external dimension < 100 nm. In addition, the Panel noted that constituent particles < 30 nm amounted to less than 1% of particles by number. The Panel therefore considered that studies with TiO2 NPs < 30 nm were of limited relevance to the safety assessment of E 171. The Panel concluded that although gastrointestinal absorption of TiO2 particles is low, they may accumulate in the body. Studies on general and organ toxicity did not indicate adverse effects with either E 171 up to a dose of 1,000 mg/kg body weight (bw) per day or with TiO2 NPs (> 30 nm) up to the highest dose tested of 100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to a dose of 1,000 mg E 171/kg bw per day, the highest dose tested in the EOGRT study. However, observations of potential immunotoxicity and inflammation with E 171 and potential neurotoxicity with TiO2 NPs, together with the potential induction of aberrant crypt foci with E 171, may indicate adverse effects. With respect to genotoxicity, the Panel concluded that TiO2 particles have the potential to induce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlation was observed between the physico-chemical properties of TiO2 particles and the outcome of either in vitro or in vivo genotoxicity assays. A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate in parallel and the relative contributions of different molecular mechanisms elicited by TiO2 particles are not known. There was uncertainty as to whether a threshold mode of action could be assumed. In addition, a cut-off value for TiO2 particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO2 NPs. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel concluded that E 171 can no longer be considered as safe when used as a food additive.
| S-EPMC8101360 | biostudies-literature
Project description: Not available
| S-EPMC11295244 | biostudies-literature
Project description:The interaction between gut microbiota and host plays a central role in health. Dysbiosis, detrimental changes in gut microbiota and inflammation have been reported in non-communicable diseases. While diet has a profound impact on gut microbiota composition and function, the role of food additives such as titanium dioxide (TiO2), prevalent in processed food, is less established. In this project, we investigated the impact of food grade TiO2 on gut microbiota of mice when orally administered via drinking water. While TiO2 had minimal impact on the composition of the microbiota in the small intestine and colon, we found that TiO2 treatment could alter the release of bacterial metabolites in vivo and affect the spatial distribution of commensal bacteria in vitro by promoting biofilm formation. We also found reduced expression of the colonic mucin 2 gene, a key component of the intestinal mucus layer, and increased expression of the beta defensin gene, indicating that TiO2 significantly impacts gut homeostasis. These changes were associated with colonic inflammation, as shown by decreased crypt length, infiltration of CD8+ T cells, increased macrophages as well as increased expression of inflammatory cytokines. These findings collectively show that TiO2 is not inert, but rather impairs gut homeostasis which may in turn prime the host for disease development.
| S-EPMC6534185 | biostudies-literature
Project description: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.
2022-04-12 | GSE186727 | GEO