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Microarrays after exposure in Caco-2 cells to titanium dioxide food additive E171 and titanium dioxide nanoparticles and microparticles


ABSTRACT: 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. Overall design: Total of 76 samples, 3 biological replicates plus every sample in duplicate. One time course exposure to TiO2 NPs for 2, 4, and 24h and exposure to MPs and E171 for 24h. Samples of MPs and E171 also have a time 0h exposure. First pre-processing was performed with the samples of the time course experiment with NPs. For this, six groups were defined: NPs 2h, 4h, and 24h for the exposed samples and control 2h, 4h, and 24h for the controls. The second pre-processing was split in 2 parts in which the first part was a pre-processing of the NPs 24h with its time-matched control and the second part was a pre-processing of E171 24h and MPs 24h with their time-matched control. The second pre-processing was split in 2 because the experiments were performed independently.

INSTRUMENT(S): Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Feature Number version)

ORGANISM(S): Homo Sapiens

SUBMITTER: Héloïse Proquin 

PROVIDER: GSE110410 | GEO | 2019-11-22

REPOSITORIES: GEO

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