Effect of combustion-derived particles on genotoxicity and telomere length: A study on human cells and exposed populations

Toxicol Lett. 2020 Apr 1:322:20-31. doi: 10.1016/j.toxlet.2020.01.002. Epub 2020 Jan 7.

Abstract

Particulate matter (PM) from combustion processes has been associated with oxidative stress to DNA, whereas effects related to telomere dysfunction are less investigated. We collected air-borne PM from a passenger cabin of a diesel-propelled train and at a training facility for smoke diving exercises. Effects on oxidative stress biomarkers, genotoxicity measured by the comet assay and telomere length in PM-exposed A549 cells were compared with the genotoxicity and telomere length in peripheral blood mononuclear cells (PBMCs) from human volunteers exposed to the same aerosol source. Although elevated levels of DNA strand breaks and oxidatively damaged DNA in terms of Fpg-sensitive sites were observed in PBMCs from exposed humans, the PM collected at same locations did not cause genotoxicity in the comet assay in A549 cells. Nevertheless, A549 cells displayed telomere length shortening after four weeks exposure to PM. This is in line with slightly shorter telomere length in PBMCs from exposed humans, although it was not statistically significant. In conclusion, the results indicate that genotoxic potency measured by the comet assay of PM in A549 cells may not predict genotoxicity in exposed humans, whereas telomere length measurements may be a novel indicator of genotoxic stress in cell cultures and humans.

Keywords: Combustion particles; Comet assay; Genotoxicity; Oxidative stress; SRM2975; Telomere length.

MeSH terms

  • A549 Cells
  • Air Pollutants, Occupational / toxicity
  • Cell Survival / drug effects
  • DNA Damage*
  • Firefighters
  • Humans
  • Inhalation Exposure / adverse effects*
  • Inhalation Exposure / analysis
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / pathology
  • Occupational Exposure / adverse effects
  • Occupational Exposure / analysis
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Particle Size
  • Particulate Matter / toxicity*
  • Smoke / adverse effects*
  • Telomere Homeostasis / drug effects*
  • Telomere Homeostasis / genetics
  • Vehicle Emissions / toxicity*

Substances

  • Air Pollutants, Occupational
  • Particulate Matter
  • Smoke
  • Vehicle Emissions