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.

Oxidative Stress and Inflammatory Biomarkers for Populations with Occupational Exposure to Nanomaterials: A Systematic Review and Meta-Analysis

“…As a result, 16 studies were excluded because of data unavailable ( n = 9), without non-exposed controls ( n = 6) and unclear exposure order for NMs and filtered air in two groups ( n = 1). Eventually, 28 studies with 2636 participants (including 1374 exposed and 1262 non-exposed) were included in the meta-analysis [ 14 , 15 , 16 , 17 , 18 , 19 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ].…”

“…Also, the increase fold of 8-OHG (SMD = 2.98) was higher than 8-OHdG (SMD = 1, which was even non-significant in the subgroup analysis) and 5-OHMeU (SMD = 1.9). Aldehydes C6-C12, 3-NOTyr and o-Tyr were only measured in NM-exposed workers [ 15 , 16 , 29 , 44 ], not in cell and animal studies. However, in line with the predicted theory, our meta-analysis also confirmed positive correlations of these three biomarkers with NM exposure.…”

“…Furthermore, the negative results of oxidative stress biomarkers in urinary samples may also be associated with the following reasons: (1) it has been reported that there is a time window to detect the responses of urinary biomarkers after exposure. If the sample is not collected in the sensitive time windows, the indicators may be seldomly changed after exposure [ 29 , 72 ]. For example, Zhang et al detected slower generation and/or urinary excretion kinetics of urinary 8-OHG and HNE in NM- exposed workers.…”

“…These two biomarkers were only significantly increased at 36 h (an acute model) or three weeks (a chronic model) post-exposure. o-Tyr and 5-OHMeU were not statistically elevated in the longest sampling time points [ 29 ]; (2) the elimination half-lives of oxidative stress biomarkers in plasma were also found to be longer than that in urine [ 73 ], which may result in their low levels in urinary samples even if the same sampling time points were set as the blood samples; (3) some oxidative stress biomarkers (e.g., HNE and other aldehydes) are intermediary oxidation products which can be fed by a precursor/parent molecule, but consumed by subsequent oxidation reactions or adduct formation. Hereby, the overall concentrations for themselves in urine may be not high; and (4) liquid chromatography electrospray ionization—mass spectrometry/mass spectrometry was used for analyses of urinary oxidative stress biomarkers in all included studies.…”

“… Forest plots assessing the effects of exposure to different NMs on the level of HNE compared with the non-exposed control group. NMs, nanomaterials; SiO 2 NPs, silica oxide nanoparticles; IONPs, iron oxide nanoparticles; TiO 2 NPs, titanium dioxide nanoparticles; HNE, 4-hydroxy-2-nonhenal; SMD, standardized mean difference; CI, confidence interval [ 15 , 18 , 29 , 31 , 33 , 34 ]. …”