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Gene expression profiling in colon of mice exposed to food additive titanium dioxide (E171)
Héloïse Proquin1, Marlon J Jetten1, Marloes C M Jonkhout1
1Department of Toxicogenomics, GROW Institute of Oncology and Developmental Biology, Maastricht University, The Netherlands.
Abstract:
Dietary factors that may influence the risks of colorectal cancer, including specific supplements, 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 tumours in vivo. This study aimed to investigate the molecular mechanisms behind these effects after 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 were studied by whole genome mRNA microarray analysis on the mice's distal colons. In addition, histopathological changes as well as a proliferation marker were analysed. The results showed significant gene expression changes in the olfactory/GPCR receptor family, oxidative stress, the immune system and of cancer related genes. Transcriptome analysis also identified genes that thus far have not been included in known biological pathways and can induce functional changes by interacting with other genes involved in different biological pathways. Histopathological analysis showed alteration and disruption in the normal structure of crypts inducing a hyperplastic epithelium. At cell proliferation level, no consistent increase over time was observed. These results may offer a mechanistic framework for the enhanced tumour growth after ingestion of E171 in BALB/c mice.
Insights
The food additive titanium dioxide (E171) may promote colorectal cancer by altering gene expression and disrupting colon structure. This study investigated E171
Area of Science:
- Gastroenterology
- Toxicology
- Molecular Biology
Background:
- Dietary factors are investigated for their role in colorectal cancer (CRC) risk.
- The food additive titanium dioxide (E171) has shown potential to damage DNA and promote CRC tumor growth in previous studies.
- Understanding the molecular mechanisms of E171's effects is crucial for assessing its safety.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the effects of E171 exposure on the colon.
- To analyze transcriptome, histopathological, and proliferation changes in mice exposed to E171.
Main Methods:
- BALB/c mice were gavaged with E171 (5 mg/kg body weight/day) for 2, 7, 14, and 21 days.
- Whole genome mRNA microarray analysis was performed on distal colon tissue.
- Histopathological analysis and proliferation marker assessment were conducted.
Main Results:
- Significant gene expression changes were observed in olfactory/GPCR receptors, oxidative stress pathways, immune system genes, and cancer-related genes.
- Novel genes interacting within biological pathways were identified.
- Histopathological analysis revealed crypt structure disruption and hyperplastic epithelium.
- No consistent increase in cell proliferation was observed over time.
Conclusions:
- E171 exposure induces significant molecular and structural changes in the mouse colon.
- These alterations provide a potential mechanistic framework for E171's role in enhancing colorectal tumor growth.
- Further research is needed to elucidate the precise pathways involved and long-term implications.