title: Titanium dioxide food additive (E171) induces ROS formation and genotoxicity: contribution of micro and nano-sized fractions.
abstract: Since 1969, the European Union approves food-grade titanium dioxide (TiO2), also known as E171 colouring food additive. E171 is a mixture of micro-sized particles (MPs) and nano-sized particles (NPs). Previous studies have indicated adverse effects of oral exposure to E171, i.e. facilitation of colon tumour growth. This could potentially be partially mediated by the capacity to induce reactive oxygen species (ROS). The aim of the present study is to determine whether E171 exposure induces ROS formation and DNA damage in an in vitro model using human Caco-2 and HCT116 cells and to investigate the contribution of the separate MPs and NPs TiO2fractions to these effects. After suspension of the particles in Hanks' balanced salt solution buffer and cell culture medium with either bovine serum albumin (BSA) or foetal bovine serum, characterization of the particles was performed by dynamic light scattering, ROS formation was determined by electron spin/paramagnetic resonance spectroscopy and DNA damage was determined by the comet and micronucleus assays. The results showed that E171, MPs and NPs are stable in cell culture medium with 0.05% BSA. The capacity for ROS generation in a cell-free environment was highest for E171, followed by NPs and MPs. Only MPs were capable to induce ROS formation in exposed Caco-2 cells. E171, MPs and NPs all induced single-strand DNA breaks. Chromosome damage was shown to be induced by E171, as tested with the micronucleus assay in HCT116 cells. In conclusion, E171 has the capability to induce ROS formation in a cell-free environment and E171, MPs and NPs have genotoxic potential. The capacity of E171 to induce ROS formation and DNA damage raises concerns about potential adverse effects associated with E171 (TiO2) in food.
authors: Department of Toxicogenomics, GROW Institute of Oncology and Developmental Biology, Maastricht University, P.O. Box 616, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands, h.proquin@maastrichtuniversity.nl.
authors: Héloïse
authors: H
authors: Proquin
authors: Unidad de Biomedicina, Facultad de Estudios Superiores (FES) Iztacala, Universidad Nacional Autonoma de Mexico (UNAM), Estado de Mexico, Mexico and.
authors: Carolina
authors: C
authors: Rodríguez-Ibarra
authors: Department of Toxicogenomics, GROW Institute of Oncology and Developmental Biology, Maastricht University, P.O. Box 616, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands.
authors: Carolyn G J
authors: CG
authors: Moonen
authors: Unidad de Biomedicina, Facultad de Estudios Superiores (FES) Iztacala, Universidad Nacional Autonoma de Mexico (UNAM), Estado de Mexico, Mexico and.|Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Estado de Mexico 04510, Mexico.
authors: Ismael M
authors: IM
authors: Urrutia Ortega
authors: Department of Toxicogenomics, GROW Institute of Oncology and Developmental Biology, Maastricht University, P.O. Box 616, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands.
authors: Jacob J
authors: JJ
authors: Briedé
authors: Department of Toxicogenomics, GROW Institute of Oncology and Developmental Biology, Maastricht University, P.O. Box 616, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands.
authors: Theo M
authors: TM
authors: de Kok
authors: Department of Toxicogenomics, GROW Institute of Oncology and Developmental Biology, Maastricht University, P.O. Box 616, Universiteitssingel 50, 6200 MD Maastricht, The Netherlands.
authors: Henk
authors: H
authors: van Loveren
authors: Unidad de Biomedicina, Facultad de Estudios Superiores (FES) Iztacala, Universidad Nacional Autonoma de Mexico (UNAM), Estado de Mexico, Mexico and.
authors: Yolanda I
authors: YI
authors: Chirino
mesh_terms: D018938:Caco-2 Cells; D003106:Colon / Q000187:drug effects; D020552:Comet Assay; D004247:DNA / Q000187:drug effects; D053904:DNA Breaks, Single-Stranded; D005503:Food Additives / Q000009:adverse effects / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000009:adverse effects* / Q000737:chemistry; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D017382:Reactive Oxygen Species; D014025:Titanium / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D005503:Food Additives; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D004247:DNA; D014025:Titanium