TiO Nanoparticles Caused DNA Damage in Lung and Extra-Pulmonary Organs Through ROS-Activated FOXO3a Signaling Pathway After Intratracheal Administration in Rats.

INTRODUCTION

Because of the increased production and application of manufactured Nano-TiO in the past several years, it is important to investigate its potential hazards. TiO is classified by IARC as a possible human carcinogen; however, the potential mechanism of carcinogenesis has not been studied clearly. The present study aimed to investigate the mechanism of DNA damage in rat lung and extra-pulmonary organs caused by TiOnanoparticles.

METHODS

In the present study, rats were exposed to Nano-TiO by intratracheal injection at a dose of 0, 0.2, or 1 g/kg body weight. The titanium levels in tissues were detected by ICP-MS. Western blot was used to detect the protein expression levels. The DNA damage and oxidative stress were detected by comet assay and ROS, , , and levels, respectively.

RESULTS

The titanium levels of the 1 g/kg group on day-3 and day-7 were significantly increased in liver and kidney as well as significantly decreased in lung compared to day-1. ROS and levels were statistically increased, whereas and levels were statistically decreased in tissues of rats in dose-dependent manners after Nano-TiO treatment. , /, and / in lung, liver, and kidney activated in dose-dependent manners. The levels of DNA damage in liver, kidney, and lung in each Nano-TiO treatment group were significantly increased and could not recover within 7 days. , , and in liver, kidney, and lung of rats exposed to Nano-TiO statistically increased, which triggered DNA repair.

CONCLUSION

This work demonstrated that Ti could deposit in lung and enter extra-pulmonary organs of rats and cause oxidative stress, then trigger DNA damage through activating the pathway and then promoting , , and to process the DNA repair.