Genotoxicity Evaluation of Titanium Dioxide Nanoparticles In Vivo and In Vitro: A Meta-Analysis

Abstract

Background: Recent studies have raised concerns about genotoxic effects associated with titanium dioxide nanoparticles (TiO2 NPs), which are commonly used. This meta-analysis aims to investigate the potential genotoxicity of TiO2 NPs and explore influencing factors. Methods: This study systematically searched Chinese and English literature. The literature underwent quality evaluation, including reliability evaluation using the toxicological data reliability assessment method and relevance evaluation using routine evaluation forms. Meta-analysis and subgroup analyses were performed using R software, with the standardized mean difference (SMD) as the combined effect value. Results: A total of 26 studies met the inclusion criteria and passed the quality assessment. Meta-analysis results indicated that the SMD for each genotoxic endpoint was greater than 0. This finding implies a significant association between TiO2 NP treatment and DNA damage and chromosome damage both in vivo and in vitro and gene mutation in vitro. Subgroup analysis revealed that short-term exposure to TiO2 NPs increased DNA damage. Rats and cancer cells exhibited heightened susceptibility to DNA damage triggered by TiO2 NPs (p < 0.05). Conclusions: TiO2 NPs could induce genotoxicity, including DNA damage, chromosomal damage, and in vitro gene mutations. The mechanism of DNA damage response plays a key role in the genotoxicity induced by TiO2 NPs.

Oral Exposure to Titanium Dioxide E171 and Zinc Oxide Nanoparticles Induces Multi-Organ Damage in Rats: Role of Ceramide

“…TiO 2 NPs and ZnO NPs have been detected in blood, tissues, and several organs including the brain, heart, intestine, kidney, liver, lung, and stomach of mice and rats after inhalation, intraperitoneal, or oral exposure [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Exposure to TiO 2 NPs and ZnO NPs can cause vascular dysfunction in subcutaneous arteries, coronary arteries, and the aorta [ 13 , 14 ]; histological and functional changes in organs [ 15 , 16 ]; genotoxicity [ 17 ]; cytotoxicity [ 18 , 19 ]; inflammation [ 20 , 21 ]; and endoplasmic reticulum (ER) stress [ 22 , 23 ]. Depending on dose and physicochemical characteristics (components, charges, solubility, size, shape), TiO 2 NPs and ZnO NPs produce reactive oxygen species (ROS), including radical and non-radical species such as peroxynitrite, activating different signaling pathways, eventually altering multiple cellular processes including mitosis, apoptosis, or autophagy [ 24 , 25 ].…”

A Systematic Genotoxicity Assessment of a Suite of Metal Oxide Nanoparticles Reveals Their DNA Damaging and Clastogenic Potential

“…Besides inflammation, MONPs have been reported to induce primary and secondary genotoxicity both in vivo and in vitro [26,27]. Primary genotoxicity is the result of direct interactions of NPs with DNA or cellular proteins involved in mitosis or via the generation of reactive oxygen species (ROS) [28].…”

Chitosan-coated titanium dioxide nanoparticles: Fabrication, characterisation and toxicological evaluation in Drosophila melanogaster

“…In rodent models like rats and mice, TiO 2 particles have demonstrated pulmonary in ammation, altered hepatic gene expressions and liver enzyme levels, decreased sperm quality and impaired fertility [8][9][10][11]. Similarly, in cell culture models, TiO 2 particles induced apoptosis and necrosis mechanisms, triggered pro-in ammatory cytokines in addition caused DNA damage, and chromosomal aberrations, raising concerns about their potential genotoxic effects [12,13]. In the Drosophila melanogaster model, TiO 2 particles demonstrated larval morphological deformities, delayed development, impaired learning and memory in adult ies and signi cant oxidative stress [14][15][16].…”