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

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.

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

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 (rS) = -0.16; p < 0.01) and MDA-hgb (rS = -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 (ß =-0.0041; p = 0.0063) and that the association between B-Pb and rTL remained significant, even when adjusting for age (ß = -0.0041; p = 0.0065) and in multivariable-adjusted model (ß = -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.

Telomere length in children environmentally exposed to low-to-moderate levels of lead.

Shorter relative telomere length in peripheral blood is a risk marker for some types of cancers and cardiovascular diseases. Several environmental hazards appear to shorten telomeres, and this shortening may predispose individuals to disease. The aim of the present cross-sectional study was to assess the effect of environmental exposure to lead on relative telomere length (rTL) in children. A cohort of 99 8-year-old children was enrolled from 2007-2010. Blood lead concentrations (B-Pb) were measured by graphite furnace atomic absorption spectrometry, and blood rTL was measured by quantitative PCR. The geometric mean of B-Pb was 3.28 µg/dl (range: 0.90-14.2), and the geometric mean of rTL was 1.08 (range: 0.49-2.09). B-Pb was significantly inversely associated with rTL in the children (rS = -0.25, p = 0.013; in further analyses both log-transformed-univariate regression analysis ß = -0.13, p = 0.026, and R(2)adj 4%; and ß = -0.12, p = 0.056 when adjusting for mothers' smoking during pregnancy, Apgar score, mother's and father's ages at delivery, sex and mother's education, R(2)adj 12%, p = 0.011). The effect of lead remained significant in children without prenatal tobacco exposure (N = 87, rS = -0.24, p = 0.024; in further analyses, ß = -0.13, p = 0.029, and R(2)adj 4%). rTL was not affected by sex, the concentrations of other elements in the blood (i.e., cadmium and selenium concentrations), or oxidative injury parameters (total antioxidant status, 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances). Lead exposure in childhood appears to be associated with shorter telomeres, which might contribute to diseases, such as cardiovascular disease. The inverse association between blood lead level and the telomeres in children emphasizes the importance of further reducing lead levels in the environment.

8-hydroxy-2'-deoxyguanosine in colorectal adenocarcinoma--is it a result of oxidative stress?

BACKGROUND: 8-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/METHODS: Samples 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. RESULTS: The 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. CONCLUSIONS: 8-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.

Effects of X-ray irradiation on methylation levels of p16, MGMT and APC genes in sporadic colorectal carcinoma and corresponding normal colonic mucosa.

BACKGROUND: Colorectal cancer, one of the most aggressive cancers, occurs with a high incidence world-wide. Cancer development and progression is dictated by a series of alterations in a number genes, e.g., tumor suppressor genes, DNA repair genes, oncogenes and others. DNA methylation is an epigenetic modification that is profoundly altered in most cancers. Radiation is a well-known genotoxic agent and human carcinogen that gives rise to a variety of long-term effects. The inheritance of genomic instability suggests the possible involvement of epigenetic mechanisms, such as changes in methylation of the cytosine residues located within CpG dinucleotides. In the current study we evaluated the effect of X-ray irradiation on methylation levels of p16, MGMT and APC genes in colorectal cancers and normal colonic mucosa. MATERIAL/METHODS: Fresh tissue samples were obtained from 28 patients (ages 26 to 81 years) with primary colorectal adenocarcinoma and corresponding normal tissues. We used methylation-specific polymerase chain reaction (MSP) for analysis of the methylation status of p16, MGMT, APC1A and APC1B genes. RESULTS: Methylation of p16, MGMT, APC1A and APC1B was detected in 42%, 67%, 42% and 20% of tumors before X-ray irradiation and in 63%, 56%, 25% and 31% after radiotherapy, respectively. In corresponding normal colonic mucosa, methylation of p16, MGMT and APC1A was detected in 17%, 25% and 8% before and in 19%, 31% and 6% after irradiation, respectively. CONCLUSIONS: Differences between groups, although noticeable, did not reach the level of statistical significance.

An evaluation of selected oral health indicators and cariogenic bacteria titer in patients with Helicobacter pylori.

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. OBJECTIVES: The aim of the present study was to investigate the prevalence and virulence of H. pylori in the oral cavity and the correlation of these factors with oral health and cariogenic bacteria titer. MATERIAL AND METHODS: The study involved 108 adults who were positive in urease tests for H. pylori presence in the gastric mucosa. Group I consisted of 50 patients with positive saliva tests using PCR for the presence of H. pylori DNA, while group II comprised 58 patients with negative tests. The research material consisted of saliva and dental plaque. To determine the density of S. mutans and Lactobacillus, commercially available S. mutans and LB sets were used. RESULTS: H. pylori DNA was found in the oral cavities of 46% of the patients who had tested positive in urease tests for the presence of these bacteria in the stomach. Among those who tested positive for the presence of H. pylori in the oral cavity, virulent strains were identified in 16% of the patients. Approximal plaque index (API) and bleeding on probing (BOP) were found to be significantly higher in patients with confirmed H. pylori in the oral cavity. This group also had a smaller number of S. mutans colonies. CONCLUSIONS: H. pylori is found more often in patients with poor oral hygiene. Oral sanitation and hygiene instructions should be considered relevant as a complement to eradication therapy.