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.
Background8-hydroxy-2′-deoxyguanosine (8-OHdG) is one of the most abundant oxidatively modified lesions in DNA and is a marker of the oxidative stress. 8-OHdG is a mutagenic lesion and it can mispair with adenine, causing G: C→T: A transversion. Our task was to determine the 8-OHdG level in patients with colorectal adenocarcinoma directly in tumor tissues and corresponding normal mucosa.Material/MethodsSamples of tumor tissues and corresponding normal mucosa of 47 patients undergoing surgery for colorectal cancer were analyzed. DNA was isolated from both tumor and normal tissues. Then, DNA was hydrolyzed to nucleotides using nuclease P1 and alkaline phosphatase. The 8-OHdG and 2′-dG (2′-deoxyguanosine) were determined in hydrolysates by high-performance liquid chromatography (HPLC) with electrochemical (EC) and UV detector.ResultsThe levels of 8-OHdG in colorectal adenocarcinoma tissues were higher than in corresponding normal mucosa. No significant differences were shown in 8-OHdG levels in the cancerous and cancer-free tissues between age and sex and stages A/B and C/D of Duke’s classification.Conclusions8-OHdG reflects the local oxidative stress in colon adenocarcinoma tissue together with ageing processes, but not the intensity of tumorigenesis itself. Because of many factors that could influence the oxidative modification of DNA bases, its role as a diagnostic and/or prognostic factor in colon adenocarcinoma seems to be limited.
Background. Studies based on polymerase chain reaction (PCR) techniques indicate that Helicobacter pylori can be constantly or temporarily present in the oral cavity in virulent or non-virulent form. Streptococcus mutans exerts a strong inhibitory effect on H. pylori.
A genetic progression model of head and neck squamous cell carcinoma (HNSCC) has not yet been elucidated, and the genetic basis for "field cancerization" has also remained unclear. Most of the "field cancerization" has been explained by the presence of cells with genetic alterations, however, involvement of epigenetic alterations in field cancerization was shown, too.In the present study, paired specimens of tumour and adjacent normal tissues were obtained from materials surgically resected from 25 patients with squamous cell carcinoma of the head and neck. After extraction of RNA, quantitative RT-PCR method using 7300 TaqMan (AppliedBiosystems) was used to analyze gene expression of MGMT, p16, TIMP3. Next, we examined the association between MGMT, p16, TIMP3 promoters methylation and genes expression. The studies demonstrated higher expression of p16 gene in tumour compared with adjacent normal tissues. Other, MGMT and TIMP3 showed no differences. Our results revealed no correlation between MGMT, p16, TIMP3 promoters methylation level and expression of these genes. Finally, we performed direct DNA sequence analysis of MGMT somatic mutations both in tumour and adjacent normal tissue. MGMT is a 300,000 bp-long gene that consist of six relatively short exons. The gene is transcribed as a 1265 bp-long mRNA, covering the 717 bp-long coding sequence. To facilitate the screening of somatic mutations in the coding region of the MGMT, a simple approach has been developed. As the gene is expressed in HNSCC, we decided to amplify the whole coding region of MGMT in two separate PCR reactions using its cDNA as a template. The amplicons of individual patients were labeled in PCR with MID identifiers and sequenced using a medium-scale next generation sequencing system, GS Junior (Roche/454). The method developed can accurately identify low-level mutations, down to a level of 5% of cells within the testing sample.The lack of progress in head and neck oncology emphasizes the importance of molecular genetic studies to define alterations that may correlate with tumor behavior. Further studies may help clarify this issue.
The aim of the present study was to compare a group of workers with stable lead levels with a group of workers with fluctuating lead levels in terms of selected hematological, biochemical, and immunological parameters. The examined group included male workers occupationally exposed to lead. Blood lead (PbB) levels were measured every 3 months during the 5-year observation. Based on standard deviation of mean PbB levels, the examined population was divided into two groups: low level of fluctuation (L-SD) and high level of fluctuation (H-SD) groups. The mean and maximal PbB levels were significantly higher in the H-SD group than in the L-SD group by 9 and 22%, respectively. At the same time, the maximal level of zinc protoporphyrin (ZPP) and standard deviation of mean ZPP level were higher in the H-SD group by 29 and 55%, respectively. The maximal level of hemoglobin and white blood cell (WBC) count as well as standard deviation of the mean hemoglobin level and WBC count were higher in the H-SD group by 2, 8, 58, and 24%, respectively. The expression of nuclear factor kappa-B1 gene and telomerase reverse transcriptase gene was significantly greater in the H-SD group than in the L-SD group by 11 and 28%, respectively. Workers occupationally exposed to lead do not represent a homogenous population. Some present stable lead levels, whereas others have fluctuating lead levels. These fluctuations are related to secondary changes in ZPP and hemoglobin levels as well as WBC count.
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