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Transcriptomics effects of ingestion of food additive titanium dioxide (E171) in the colon of BALB/c mice

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE92563 | GEO | 2018/01/24

REPOSITORIES: GEO

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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

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Transcriptomics effects of ingestion of food additive titanium dioxide (E171) in the colon of BALB/c mice

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