Maternal inhalation of surface-coated nanosized titanium dioxide (UV-Titan) in C57BL/6 mice: effects in prenatally exposed offspring on hepatic DNA damage and gene expression

Abstract

We investigated effects of maternal pulmonary exposure to titanium dioxide (UV-Titan) on prenatally exposed offspring. Time-mated mice (C57BL/6BomTac) were inhalation exposed (1 h/day to 42 mg UV-Titan/m³ aerosolised powder or filtered air) during gestation days (GDs) 8–18. We evaluated DNA strand breaks using the comet assay in bronchoalveolar lavage (BAL) cells and livers of the time-mated mice (5 and 26–27 days after inhalation exposure), and in livers of the offspring (post-natal days (PND) 2 and 22). We also analysed hepatic gene expression in newborns using DNA microarrays. UV-Titan exposure did not induce DNA strand breaks in time-mated mice or their offspring. Transcriptional profiling of newborn livers revealed changes in the gene expression related to the retinoic acid signalling pathway in the females, while gene expression in male offspring was unaffected. Changes may be a secondary response to maternal inflammation although no direct link was evident through gene expression analysis.

Keywords::

• In utero exposure
• lung inflammation
• DNA strand breaks
• retinoic acid pathway
• acute-phase response

Acknowledgements

Technical assistance from Gitte Kristiansen, Michael Guldbrandsen, Lourdes Petersen, Margit Frederiksen, Anne-Mette Z. Boisen and Dongmei Wu is greatly appreciated. The study was supported by the Danish Agency for Science, Technology and Innovation; the Danish Working Environment Research Fund (Nanokem); ISMF; the Danish Research Council; and Health Canada A-Base funds. The Danish Association of the Paint and Lacquer industry supplied the particles.