8-hydroxyguanine and titanium-dioxide

Inhaled particulate matter (PM) might influence many adverse health effects in human body, including increased exacerbations of pulmonary and cardiovascular diseases. In this study, we examined the associations between PM and pulmonary adverse effects. Two types of particles, Asian dust (AD) and titanium dioxide (TiO(2)), were administered intratracheally to C57BL/6 mice. The mice were exposed to saline and saline suspensions of 20 mg/kg of AD, TiO(2) particles twice a week for 12 weeks. Following exposure with these particles, the lungs were analyzed histopathologically by hematoxylin and eosin (H&E) and Masson's trichrome (MT) staining. Oxidative injuries were determined by immunohistochemistry (IHC) for 8-oxoguanine in the lungs and Comet assays in peripheral blood mononuclear cells (PBMCs) of C57BL/6 mice. Mice exposed to AD and TiO(2) showed significant inflammatory changes and oxidative damages in the lungs as compared with the control group. DNA damage in PBMCs was also increased significantly in AD and TiO(2)-exposed mice. However, lung fibrosis was minimal and there was no significant difference between PM exposed and control mice. Exposure to AD and TiO(2) particles-induced similar inflammatory damages in the lungs and elicited oxidative DNA damage in the PBMCs.

Topics: Air Pollutants; Animals; Comet Assay; DNA Damage; Dust; Fibrosis; Guanine; Inflammation; Leukocytes, Mononuclear; Lung; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Particle Size; Particulate Matter; Titanium

TiO(2) is considered to be toxicologically inert, at least under nonoverload conditions. To study if there are differences in lung effects of surface treated or untreated TiO(2) we investigated the inflammatory and genotoxic lung effects of two types of commercially available TiO(2) at low doses relevant to the working environment. Rats were exposed by instillation to a single dose of 0.15, 0.3, 0.6, and 1.2 mg of TiO(2) P25 (untreated, hydrophilic surface) or TiO(2) T805 (silanized, hydrophobic surface) particles, suspended in 0.2 ml of physiological saline supplemented with 0.25% lecithin. As control, animals were instilled with the vehicle medium only or with a single dose of 0.6 mg quartz DQ12. At days 3, 21, and 90 after instillation bronchoalveolar lavage was performed and inflammatory signs such as cells, protein, tumor necrosis factor-alpha, fibronectin, and surfactant phospholipids were determined. Additionally, 8 microm frozen sections of the left lobe of the lung were cut and stored at -80 degrees C. The sections were used for immunohistochemical detection of 8-oxoguanine (8-oxoGua) by a polyclonal antibody in the DNA of individual lung cells. In the quartz-exposed animals a strong progression in the lung inflammatory response was observed. Ninety days after exposure a significant increase in the amount of 8-oxoGua in DNA of lung cells was detected. In contrast, animals exposed to TiO(2) P25 or TiO(2) T805 showed no signs of inflammation. The amount of 8-oxoGua as a marker of DNA damage was at the level of control. The results indicate that both types of TiO(2) are inert at applicated doses.

Topics: Air Pollutants, Occupational; Animals; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Cell Count; Cell Division; DNA Damage; Dose-Response Relationship, Drug; Female; Guanine; Instillation, Drug; Lung; Mutagens; Particle Size; Pneumonia; Pulmonary Surfactants; Quartz; Rats; Rats, Wistar; Surface Properties; Titanium