Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse

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Abstract

Background

Nanotechnology is developing rapidly throughout the world and the production of novel man-made nanoparticles is increasing, it is therefore of concern that nanomaterials have the potential to affect human health. The purpose of this study was to investigate the effects of maternal exposure to nano-sized anatase titanium dioxide (TiO ₂) on gene expression in the brain during the developmental period using cDNA microarray analysis combined with Gene Ontology (GO) and Medical Subject Headings (MeSH) terms information.

Results

Analysis of gene expression using GO terms indicated that expression levels of genes associated with apoptosis were altered in the brain of newborn pups, and those associated with brain development were altered in early age. The genes associated with response to oxidative stress were changed in the brains of 2 and 3 weeks old mice. Changes of the expression of genes associated with neurotransmitters and psychiatric diseases were found using MeSH terms.

Conclusion

Maternal exposure of mice to TiO ₂nanoparticles may affect the expression of genes related to the development and function of the central nervous system.

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Most cited references 27

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Fetal nutrition and cardiovascular disease in adult life.

D. J. Barker, P Gluckman, K. Godfrey … (1993)

Babies who are small at birth or during infancy have increased rates of cardiovascular disease and non-insulin-dependent diabetes as adults. Some of these babies have low birthweights, some are small in relation to the size of their placentas, some are thin at birth, and some are short at birth and fail to gain weight in infancy. This paper shows how fetal undernutrition at different stages of gestation can be linked to these patterns of early growth. The fetuses' adaptations to undernutrition are associated with changes in the concentrations of fetal and placental hormones. Persisting changes in the levels of hormone secretion, and in the sensitivity of tissues to them, may link fetal undernutrition with abnormal structure, function, and disease in adult life.

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Manufactured Nanomaterials (Fullerenes, C60) Induce Oxidative Stress in the Brain of Juvenile Largemouth Bass

Eva Oberdörster (2004)

Although nanotechnology has vast potential in uses such as fuel cells, microreactors, drug delivery devices, and personal care products, it is prudent to determine possible toxicity of nanotechnology-derived products before widespread use. It is likely that nanomaterials can affect wildlife if they are accidentally released into the environment. The fullerenes are one type of manufactured nanoparticle that is being produced by tons each year, and initially uncoated fullerenes can be modified with biocompatible coatings. Fullerenes are lipophilic and localize into lipid-rich regions such as cell membranes in vitro, and they are redox active. Other nano-sized particles and soluble metals have been shown to selectively translocate into the brain via the olfactory bulb in mammals and fish. Fullerenes (C60) can form aqueous suspended colloids (nC60); the question arises of whether a redox-active, lipophilic molecule could cause oxidative damage in an aquatic species. The goal of this study was to investigate oxyradical-induced lipid and protein damage, as well as impacts on total glutathione (GSH) levels, in largemouth bass exposed to nC60. Significant lipid peroxidation was found in brains of largemouth bass after 48 hr of exposure to 0.5 ppm uncoated nC60. GSH was also marginally depleted in gills of fish, and nC60 increased water clarity, possibly due to bactericidal activity. This is the first study showing that uncoated fullerenes can cause oxidative damage and depletion of GSH in vivo in an aquatic species. Further research needs to be done to evaluate the potential toxicity of manufactured nanomaterials, especially with respect to translocation into the brain.

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Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells.

Jia-Ran Gurr, Alexander Wang, Chien-Hung Chen … (2005)

Ultrafine titanium dioxide (TiO(2)) particles have been shown to exhibit strong cytotoxicity when exposed to UVA radiation, but are regarded as a biocompatible material in the absence of photoactivation. In contrast to this concept, the present results indicate that anatase-sized (10 and 20 nm) TiO(2) particles in the absence of photoactivation induced oxidative DNA damage, lipid peroxidation, and micronuclei formation, and increased hydrogen peroxide and nitric oxide production in BEAS-2B cells, a human bronchial epithelial cell line. However, the treatment with anatase-sized (200 and >200 nm) particles did not induce oxidative stress in the absence of light irradiation; it seems that the smaller the particle, the easier it is for the particle to induce oxidative damage. The photocatalytic activity of the anatase form of TiO(2) was reported to be higher than that of the rutile form. In contrast to this notion, the present results indicate that rutile-sized 200 nm particles induced hydrogen peroxide and oxidative DNA damage in the absence of light but the anatase-sized 200nm particles did not. In total darkness, a slightly higher level of oxidative DNA damage was also detected with treatment using an anatase-rutile mixture than with treatment using either the anatase or rutile forms alone. These results suggest that intratracheal instillation of ultrafine TiO(2) particles may cause an inflammatory response.

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Author and article information

Journal

Journal ID (nlm-ta): Part Fibre Toxicol

Title: Particle and Fibre Toxicology

Publisher: BioMed Central

ISSN (Electronic): 1743-8977

Publication date Collection: 2009

Publication date (Electronic): 29 July 2009

Volume: 6

Page: 20

Affiliations

[1 ]Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan

[2 ]Research Center for Health Sciences of Nanoparticles, Research Institute for Science and Technology, Tokyo University of Science, Yamazaki 2641, Noda-shi, Chiba 278-8510, Japan

Article

Publisher ID: 1743-8977-6-20

DOI: 10.1186/1743-8977-6-20

PMC ID: 2726979

PubMed ID: 19640265

SO-VID: 72adf522-4739-4159-b17d-2ff2b7ef3a80

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse

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Journal of the Netherlands Society of Toxicology

Most cited references 27

Fetal nutrition and cardiovascular disease in adult life.

Manufactured Nanomaterials (Fullerenes, C60) Induce Oxidative Stress in the Brain of Juvenile Largemouth Bass

Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells.

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