No oxidative stress or DNA damage in peripheral blood mononuclear cells after exposure to particles from urban street air in overweight elderly

Abstract

Exposure to traffic-related particulate matter (PM) has been associated with increased risk of lung disease, cancer and cardiovascular disease especially in elderly and overweight subjects. The proposed mechanisms involve intracellular production of reactive oxygen species (ROS), inflammation and oxidation-induced DNA damage studied mainly in young normal-weight subjects. We performed a controlled cross-over, randomised, single-blinded, repeated-measure study where 60 healthy subjects (25 males and 35 females) with age 55–83 years and body mass index above 25kg/m2 were exposed for 5h to either particle-filtered or sham-filtered air from a busy street with number of concentrations and PM2.5 levels of 1800/cm3 versus 23 000/cm3 and 3 µg/m3 versus 24 µg/m3, respectively. Peripheral blood mononuclear cells (PBMCs) were collected and assayed for production of ROS with and without ex vivo exposure to nanosized carbon black as well as expression of genes related to inflammation (chemokine (C-C motif) ligand 2, interleukin-8 and tumour necrosis factor), oxidative stress response (heme oxygenase (decycling)-1) and DNA repair (oxoguanine DNA glycosylase). DNA strand breaks and oxidised purines were assayed by the alkaline comet assay. No statistically significant differences were found for any biomarker immediately after exposure to PM from urban street air although strand breaks and oxidised purines combined were significantly associated with the particle number concentration during exposure. In conclusion, 5h of controlled exposure to PM from urban traffic did not change the gene expression related to inflammation, oxidative stress or DNA repair, ROS production or oxidatively damaged DNA in PBMCs from elderly overweight human subjects.

Health effects of exposure to diesel exhaust in diesel-powered trains

“…Personal exposure to UFP, obtained by bicycling in streets with heavy traffic, was positively associated with levels of Fpg-sensitive sites in PBMCs, whereas there was no effect on levels of DNA strand breaks [49]. On the other hand, elderly and overweight subjects had unaltered levels of DNA strand breaks and Fpg-sensitive sites after exposure to urban street air in a controlled exposure study, whereas the total number of DNA lesions was positively associated with the particle number concentration [50]. Studies on high-dose exposure in animals have demonstrated mixed results for the association between pulmonary exposure to DEP and DNA strand breaks in lung tissue with certain studies showing increased levels of DNA damage [51–53] and no effect [54–56].…”

Application of the comet assay in human biomonitoring: An hCOMET perspective

“…Examples of studies that have employed gradients in air pollution levels come from studies in Denmark where personal exposure to levels of ultrafine particles from traffic correlated with levels of Fpg-sensitive sites in PBMCs [66,67]. The same research group has reported that traffic-related air pollution in a chamber was associated with higher levels of DNA damage in PBMCs [68], whereas short-term exposure to even a high concentration of diesel exhaust (276 mg/m 3 for 3 h) had no effect on DNA strand breaks or oxidatively damaged DNA in PBMCs [69]. Wood smoke is another important source of particulate matter, which is increasingly relevant as an environmental exposure with the increasing number of wildfires.…”

Predictive and Prognostic Biomarkers of Respiratory Diseases due to Particulate Matter Exposure

“…It has been reported that 8-oxo-2′-deoxyguanosine (8-OHdG) is a biomarker of DNA damage 88,94. 8-OHdG is one of several oxidative damage markers.…”

“…Transition metals generates excessive ROS, which significantly increases oxidative stress 95,96. Formatted 8-OHdG causes DNA damage and mediate the cytotoxicity and carcinogenicity 88. LINE-1, one of oxidative damage-related markers, has been suggested as a gene expression and DNA methylation markers 71,72,97.…”

“…Other markers, such as Arthrobacter luteus restriction endonuclease (Alu) and TLR-4, also alters their gene expression levels in response to ambient particles 97. In addition, 8-oxoguanine DNA glycosylase (OGG1) is regarded as a DNA methylation biomarker based on previous studies 88. Takano et al98 have demonstrated that cytochrome P450 1A1 is induced by DEP exposure in the lung.…”