Telomere length, telomerase expression, and oxidative stress in lead smelters

Abstract

The negative health effects caused by lead (Pb) exposure are widely recognized; however, the molecular mechanisms remain unknown. The aim of this study was to assess the effect of occupational Pb exposure on telomere length and to investigate the potential mechanisms leading to telomere shortening. A cohort of 334 male Pb smelters (exposed group) and 60 age-adjusted males unexposed to Pb (control group) were examined. Assessments of relative telomere length (rTL) and telomerase reverse transcriptase (TERT) gene expression were performed using quantitative real-time polymerase chain reactions. Assessments of whole blood Pb (B-Pb) and whole blood cadmium (B-Cd) concentrations and serum selenium concentration (S-Se) were performed using graphite furnace atomic absorption spectrometry. We analyzed total oxidation status (TOS), lipid hydroperoxides (LHPs), malonylodialdehyde levels in serum (MDA) and in erythrocyte hemolysates (MDA-hgb), and 8-hydroxy-deoxy-guanosine (8-OHdG). The Pb-exposed group had higher B-Pb values and shorter rTL than the control group. The arithmetic mean values calculated for B-Pb were 33 µg/dL versus 2.2 µg/dL (p < 0.0001), and the rTL values were 0.928 and 1.126 relative units (p = 0.001), respectively, for the Pb-exposed and control groups. The rTL was found to gradually shorten in response to the increasing levels of Pb exposure. The Pb-exposed group also demonstrated a higher level of oxidative stress than the control group, which was indicated by increased TOS and MDA-hgb values. rTL was negatively associated with parameters that indicated increased oxidative stress, including TOS (Spearman's rank coefficient (r) = -0.16; p < 0.01) and MDA-hgb (r = -0.17; p < 0.001). No correlations were found between rTL and B-Cd and S-Se or smoking and MDA and LHP levels. Univariate analysis indicated that B-Pb was associated with decreased rTL (β =-0.0041; p = 0.0063) and that the association between B-Pb and rTL remained significant, even when adjusting for age (β = -0.0041; p = 0.0065) and in multivariable-adjusted model (β = -0.0042; p = 0.0063). In conclusion, occupational Pb exposure resulted in decreased rTL and may represent a mechanism that contributes to Pb-related diseases.

Ageing at the level of telomeres in association to residential landscape and air pollution at home and work: a review of the current evidence

“…112 Short TL in both battery plant workers and lead smelters with increasing levels of blood-lead has been reported. 113,114 In 8-year old children a similar negative association was observed between TL and blood lead concentrations. 115…”

Restoration of Mitochondrial Integrity, Telomere Length, and Sensitivity to Oxidation by In Vitro Culture of Fuchs' Endothelial Corneal Dystrophy Cells

“…Telomeric DNA, however, is highly sensitive to oxidative damage, which causes telomeric shortening and accelerates cellular senescence and cell death. 15,44 Because of the significant role of oxidative stress in FECD, we investigated telomere lengths in corneal endothelial cells from FECD and from healthy subjects. Once telomere erosion reaches a certain threshold, the cell enters a senescent state or exhibits chromosomic aberrations.…”

“…[12][13][14] Telomeric DNA is also sensitive to oxidative damage, which induces telomeric shortening, acceleration of cellular senescence, and impaired cell function. 15,16,17 Several observations indicate that FECD cells are poorly protected against oxidative stress. (1) The DJ-1 protein, known to protect against oxidative damage, is downregulated in FECD.…”

The analysis of blood lead levels changeability over the 5-year observation in workers occupationally exposed to lead

“…RNA was extracted from peripheral whole blood (500 mL) as previously described (Pawlas et al, 2015) using the GeneJET Whole Blood RNA Purification Mini Kit (Thermo Fisher Scientific, Vilnius, Lithuania) and was stored at À80 C. The quality of the RNA was assessed using electrophoresis and the Agilent 2100 Bioanalyzer (Agilent Technologies, Waldbronn, Germany). The RNA samples were reverse transcribed using the Maxima First Strand cDNA Synthesis Kit for quantitative reverse transcription polymerase chain reaction (RT-qPCR) to obtain complementary DNA (cDNA) (Thermo Fisher Scientific).…”