Gene expression profiling in colon of mice exposed to food additive titanium dioxide (E171)

HeloIse Proquin*, Marlon J. Jetten, Marloes C. M. Jonkhout, Luis G. Garduno-Balderas, Jacob J. Briede, Theo M. de Kok, Yolanda I. Chirino, Henk van Loveren

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Web of Science)

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/kg(bw)/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.
Original languageEnglish
Pages (from-to)153-165
Number of pages13
JournalFood and Chemical Toxicology
Volume111
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Titanium dioxide
  • Colorectal cancer
  • Transcriptomics
  • Mouse colon
  • Nanomaterials
  • Food additive E171
  • OXIDATIVE DNA-DAMAGE
  • COLORECTAL-CANCER
  • CARCINOMA CELLS
  • DOWN-REGULATION
  • IN-VITRO
  • NANOPARTICLES
  • RECEPTOR
  • SEROTONIN
  • CYTOTOXICITY
  • PRODUCTS

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