Elevated Urinary Biomarkers of Oxidative Damage in Photocopier Operators following Acute and Chronic Exposures

Abstract

Inhalation exposures to nanoparticles (NPs) from printers and photocopiers have been associated with upper airway and systemic inflammation, increased blood pressure, and cases of autoimmune and respiratory disorders. In this study we investigate oxidative stress induced by exposures to copier-emitted nanoparticles using a panel of urinary oxidative stress (OS) biomarkers representing DNA damage (8-hydroxydeoxyguanosine, 8-OHdG; 8-hydroxyguanosine, 8-OHG; 5-hydroxymethyl uracil 5-OHMeU), lipid peroxidation (8-isoprostane; 4-hydroxynonenal, HNE), and protein oxidation biomarkers (o-tyrosine, 3-chlorotyrosine, and 3-nitrotyrosine) under conditions of acute (single 6 h exposure, 9 volunteers, 110 urine samples) and chronic exposures (6 workers, 11 controls, 81 urine samples). Urinary biomarkers were quantified with liquid chromatography–tandem mass spectrometry after solid phase extraction sample cleanup. 8-OHdG, 8-OHG, 8-isoprostane, and HNE were significantly elevated in both the acute and chronic exposure study participants relative to the controls. In the acute exposure study, the geometric mean ratios post-/pre-exposure were 1.42, 1.10, 2.0, and 2.25, respectively. Urinary 8-OHG and HNE increased with time to at least 36 h post-exposure (post-/pre-exposure GM ratios increased to 3.94 and 2.33, respectively), suggesting slower generation and/or urinary excretion kinetics for these biomarkers. In chronically exposed operators, the GM ratios of urinary biomarkers relative to controls ranged from 1.52 to 2.94, depending on the biomarker. O-Tyrosine and 5-OHMeU biomarkers were not significantly different from the controls. 3-chlorotyrosine and 3-nitrotyrosine were not detected in the urine samples. We conclude that NPs from photocopiers induce systemic oxidative stress by damaging DNA, RNA, and lipids. Urinary levels of 8-OHdG, 8-OHG, HNE, and 8-isoprostane were orders of magnitude higher than in nanocomposite processing workers, comparable to nano titanium dioxide and fiberglass manufacturing workers, but much lower than in shipyard welding and carbon nanotube synthesis workers. Biomarkers 8-OHdG, 8-OHG, 8-isoprostane, and HNE appear to be more sensitive and robust urinary biomarkers for monitoring oxidative stress to NPs from photocopiers.

Keywords

• oxidative stress
• copier emitted nanoparticles
• oxidative stress biomarkers
• acute exposure
• chronic exposure
• reactive oxygen species