“…With regard to the pathway analyses applied in the previous study 16 , the affected biological mechanisms per time point were studied using the Consensus Pathway Database (CPDB) database for 2 different pathway analyses: over-representation gene set analysis (ORA) and a gene-set enrichment analysis (GSEA). The ORA resulted in 4 pathways after 2 days, the number of pathways increased at day 7 up to a total of 67 pathways and decreased after 14 and 21 days with 40 and 12 pathways respectively (Table 2 ).…”
Section: Resultsmentioning
confidence: 99%
“…In all pathways, 66% of the genes were up-regulated. In these pathways 6 genes were related to cancer like pancreas cancer (Ramp1 and Cckbr) 16 , 18 , 19 , melanoma (Plcb4) 20 , cervical and ovarian (Adcyap1 and Trpc3) 21 , 22 , and colorectal cancer (Ptger3) 23 . Figure 2 Visualisation of genes and pathways affected after E171 exposure.…”
Section: Resultsmentioning
confidence: 99%
“…In addition, we identified that a decrease in number of goblet cells and neoplastic alterations in distal colon of mice began after 4 weeks of exposure to TiO 2 15 . We also investigated initial transcriptome changes in colon tissue before the neoplastic alterations appeared and found that intragastric exposure to 5 mg/kg bw /day of E171 for 2, 7, 14 and 21 days led to the up-regulation of genes involved in activation of inflammation, reduction of immune capacity and up-regulation of genes related in the development of CRC 16 . In line with our data, Bettini et al .…”
Titanium dioxide as a food additive (E171) has been demonstrated to facilitate growth of chemically induced colorectal tumours in vivo and induce transcriptomic changes suggestive of an immune system impairment and cancer development. The present study aimed to investigate the molecular mechanisms behind the tumour stimulatory effects of E171 in combination with azoxymethane (AOM)/dextran sodium sulphate (DSS) and compare these results to a recent study performed under the same conditions with E171 only. BALB/c mice underwent exposure to 5 mg/kgbw/day of E171 by gavage 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.
“…With regard to the pathway analyses applied in the previous study 16 , the affected biological mechanisms per time point were studied using the Consensus Pathway Database (CPDB) database for 2 different pathway analyses: over-representation gene set analysis (ORA) and a gene-set enrichment analysis (GSEA). The ORA resulted in 4 pathways after 2 days, the number of pathways increased at day 7 up to a total of 67 pathways and decreased after 14 and 21 days with 40 and 12 pathways respectively (Table 2 ).…”
Section: Resultsmentioning
confidence: 99%
“…In all pathways, 66% of the genes were up-regulated. In these pathways 6 genes were related to cancer like pancreas cancer (Ramp1 and Cckbr) 16 , 18 , 19 , melanoma (Plcb4) 20 , cervical and ovarian (Adcyap1 and Trpc3) 21 , 22 , and colorectal cancer (Ptger3) 23 . Figure 2 Visualisation of genes and pathways affected after E171 exposure.…”
Section: Resultsmentioning
confidence: 99%
“…In addition, we identified that a decrease in number of goblet cells and neoplastic alterations in distal colon of mice began after 4 weeks of exposure to TiO 2 15 . We also investigated initial transcriptome changes in colon tissue before the neoplastic alterations appeared and found that intragastric exposure to 5 mg/kg bw /day of E171 for 2, 7, 14 and 21 days led to the up-regulation of genes involved in activation of inflammation, reduction of immune capacity and up-regulation of genes related in the development of CRC 16 . In line with our data, Bettini et al .…”
Titanium dioxide as a food additive (E171) has been demonstrated to facilitate growth of chemically induced colorectal tumours in vivo and induce transcriptomic changes suggestive of an immune system impairment and cancer development. The present study aimed to investigate the molecular mechanisms behind the tumour stimulatory effects of E171 in combination with azoxymethane (AOM)/dextran sodium sulphate (DSS) and compare these results to a recent study performed under the same conditions with E171 only. BALB/c mice underwent exposure to 5 mg/kgbw/day of E171 by gavage 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.
“…A relatively large proportion of the DEG could not be linked to known molecular pathways which indicate that E171 is affecting the biological response beyond currently known processes (Figure 3, in Ref. [3]) .…”
We investigated gene expression responses in BALB/c mice exposed by gavage to 5 mg/kg bw/day of E171 for 2, 7, 14 and 21 days. Food additive E171 (titanium dioxide) has been shown to induce oxidative stress and DNA damage in vitro as well as facilitating growth of colorectal tumours in vivo. Full genome expression changes of the colon of mice were investigated by using Agilent SurePrint G3 mouse Gene exp 60kv2 microarrays slides. The data presented in this DiB include all differentially expressed for each time point with EntrezGeneID, gene symbols, gene names and Log2FC as well as genes included in pathways after over-representation analysis in ConsensusPathDataBase. The functions of these genes in relation to the colon were described in our associated article (Proquin et al., 2017 in press) [1]. Raw and normalized gene expression data are available through NCBI GEO (GEO accession: GSE92563).
“…14 These effects are associated with the deregulated expression of genes involved in inflammatory, immunological, and specific cancer-related pathways. 15 Moreover, in vitro, E171 and TiO 2 -NPs induce damage to DNA, including base oxidation, 3 strand breaks, and chromosomal damage, 16 via oxidative mechanisms. 3,16 The role of the intestine is to absorb nutrients and water, and to protect the organism from external pathogens and harmful substances.…”
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