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CAT C-262T and GPX1 Pro198Leu polymorphisms in a Turkish population

Oxidative stress is believed to play an important role in the pathogenesis of considerable number of complex diseases. The antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPX) are important components of cell defense against oxidative stress, and polymorphisms in the genes which regulate their expression may contribute to differences in susceptibility of individuals to oxidative damage caused by reactive oxygen species. The aim of this study was to assess the distribution of CAT C-262T and GPX1 Pro198Leu genotypic variants in a Turkish population. Genotyping analyses of CAT and GPX1 were conducted in 250 unrelated, healthy volunteers by the PCR-RFLP assay. The allele frequencies were 0.784 (C) and 0.216 (T) for CAT and 0.636 (C) and 0.364 (T) for GPX1 Pro198Leu. The genotype frequencies were 0.632 (CC), 0.304 (CT), and 0.064 (TT) for CAT and 0.416 (CC), 0.44 (CT), and 0.144 (TT) for GPX1 Pro198Leu. The genotype frequencies did not deviate from Hardy–Weinberg equilibrium. The results are compared with those of other reported populations. They showed marked ethnic group differences.

Human environmental and occupational exposures to boric acid: reconciliation with experimental reproductive toxicity data.

The reproductive toxicity of boric acid and borates is a matter of current regulatory concern. Based on experimental studies in rats, no-observed-adverse-effect levels (NOAELs) were found to be 17.5 mg boron (B)/kg body weight (b.w.) for male fertility and 9.6 mg B/kg b.w. for developmental toxicity. Recently, occupational human field studies in highly exposed cohorts were reported from China and Turkey, with both studies showing negative results regarding male reproduction. A comparison of the conditions of these studies with the experimental NOAEL conditions are based on reported B blood levels, which is clearly superior to a scaling according to estimated B exposures. A comparison of estimated daily B exposure levels and measured B blood levels confirms the preference of biomonitoring data for a comparison of human field studies. In general, it appears that high environmental exposures to B are lower than possible high occupational exposures. The comparison reveals no contradiction between human and experimental reproductive toxicity data. It clearly appears that human B exposures, even in the highest exposed cohorts, are too low to reach the blood (and target tissue) concentrations that would be required to exert adverse effects on reproductive functions.

Assessment of DNA integrity (COMET assay) in sperm cells of boron-exposed workers

An extension of a male reproductive study conducted in a boric acid/borate production zone at Bandırma, Turkey, is presented. The relation between DNA-strand breaks (COMET assay, neutral and alkaline version) in sperm cells and previously described sperm quality parameters was investigated in boron-exposed males. A correlation between blood boron levels and mean DNA-strand breaks in sperm was weak, and DNA-strand breaks in sperm were statistically not different between control and exposed groups. Therefore, increasing boron exposures had no additional contribution in addition to already pre-existing DNA-strand breaks in the sperm cells. Weak but statistically significant correlations between DNA-strand breaks and motility/morphology parameters of sperm samples were observed in the neutral version of the COMET assay, while correlations between the same variables were statistically not significant in the alkaline version. A likely reason for these negative results, even in highly exposed humans, is that experimental exposures that had led to reproductive toxicity in animals were significantly higher than any boron exposures, which may be reached under realistic human conditions.

Influence of δ-aminolevulinic acid dehydratase (ALAD) polymorphism on the frequency of sister chromatid exchange (SCE) and the number of high-frequency cells (HFCs) in lymphocytes from lead-exposed workers

In this study, the cytogenetic response to lead exposure in storage battery manufacturing workers carrying different alleles of delta-aminolevulinic acid dehydratase (ALAD 1 and ALAD 2) was evaluated. The cytogenetic response was measured by analysis of the frequency of sister chromatid exchange (SCE) and the number of high-frequency cells (HFCs) in peripheral blood lymphocytes from workers occupationally exposed to lead. A total of 71 voluntary male workers were enrolled in the study. According to our genotype analysis, 50 workers had the ALAD 1-1 genotype and 21 workers had the ALAD 1-2 genotype. In spite of the statistically insignificant difference in mean values of SCE per cell between ALAD 1-1 and ALAD 1-2 workers, the percentage of HFC (HFC (%)) was statistically (chi2-test, P<0.05) higher in ALAD 1-1 workers. The control group was selected among voluntary male office workers (n = 20) and genotyping was also performed for this group in order to rule out the possibility that ALAD 1-1 subjects had a higher HFC (%) than ALAD 1-2 carriers, independent of the exposure to lead. Accordingly, 11 control workers had the ALAD 1-1 genotoype and 9 workers had ALAD 1-2. The differences in mean values of SCE per cell and HFC (%) were not statistically significant when the two genotypes in the control group were compared. On the basis of this result we suggest that ALAD 1-1 subjects might be more susceptible to cytogenetic effects of lead exposure than ALAD 1-2 subjects. There were no ALAD 2-2 subjects in the exposed and control groups.

The role of GSTM1 and GSTT1 polymorphisms in head and neck cancer risk.

Head and neck cancer (HNC) is a serious health problem worldwide and tobacco smoke is a main causative factor for this malignancy. Interindividual genetic differences in enzymes involved in the metabolism of tobacco smoke carcinogens are one of the most important risk factors in the development of HNC. GSTM1 and GSTT1 enzymes participate in detoxifying of tobacco smoke carcinogens and have deletion polymorphisms. We performed a case control study to investigate a possible association between GSTM1 and GSTT1 variants and HNC risk. A total of 98 HNC cases, all of which were squamous cell carcinoma, and 120 healthy controls were investigated. GSTM1 and GSTT1 polymorphisms were genotyped using PCR. There was a significant association between HNC and GSTM1-null genotype (adjusted OR: 2.36, 95% CI: 1.303-4.26, p = 0.005). The frequency overall of GSTT1-null genotypes was not significant in HNC patients compared with that of GSTT1-positive genotypes (adjusted OR: 1.16, 95% CI: 0.563-2.397, p = 0.686). No combined effect was observed for GSTM1 and GSTT1 genotypes. When data were stratified by smoking status, cases having GSTM1-null genotype who were smokers conferred the highest risk (adjusted OR: 4.06, 95% CI: 1.3-12.63). Thus, our results suggest that GSTM1 polymorphism may significantly increase the risk of HNC and there is an additive interaction between GSTM1-null genotype and smoking on HNC risk.

Biological monitoring of lead in workers exposed to tetraethyllead

The excretion of inorganic, and total lead was investigated in the urine of workers who were exposed to tetraethyllead (TEL) at gasoline stations. Concentrations of total and inorganic lead after chelation-extraction were determined by flame atomic absorption spectrophotometry (FAAS) in combination with a slotted quartz tube. The limit of detection was 5.2 x 10(-3) micrograms Pb/ml; average total lead and inorganic lead concentrations in the urine of workers were 79.0 (range 22.6-158.9 micrograms Pb/g creatinine) and 37.3 micrograms Pb/g creatinine (range 5.1-121.0), respectively. In the control group, the mean of the urinary total lead and inorganic lead levels were 5.5 and 3.9 micrograms Pb/g creatinine, respectively. The difference between total and inorganic lead concentrations could be due to organic lead present in the urine.

Molecular Analysis of δ-Aminolevulinic Acid Dehydratase (ALAD) Gene Polymorphism in a Turkish Population

Abstractδ-Aminolevulinic acid dehydratase (ALAD) is a cytosolic enzyme in the heme biosynthetic pathway. ALAD is a polymorphic enzyme showing marked ethnic group differences. In this study, ALAD polymorphism is studied in a Turkish population. Genomic DNA extracted from 230 individuals and polymerase chain reaction (PCR) coupled with the restriction fragment length polymorphism (RFLP) technique were used to identify variants. The frequencies of the alleles ALAD1 and ALAD2 in Turkey were 0.887 and 0.113, respectively. This study provides the first analysis of the allele frequency distribution of the ALAD gene in a Turkish population. The results are compared with other world populations.

Evaluation of Increased Proportion of Cells with Unusually High Sister Chromatid Exchange Counts as a Cytogenetic Biomarker for Lead Exposure

Sister chromatid exchange (SCE) frequency and high-frequency cells (HFCs) were analyzed in 50 storage battery plant workers with mean blood lead level (BLL) of 40.14±9.99 μg/dL. The mean BLL in the control group (n=30) was 9.77±1.67 μg/dL. This difference in mean BLLs between control and exposed group was statistically significant (p<0.05) and reflects clearly the lead exposure in the workers. Urinary aminolevulinic acid (U-ALA) was also determined in both control (3.37±0.89 mg ALA/g creatinine) and exposed groups (12.39±6.18 mg ALA/g creatinine) and U-ALA excretion was statistically higher (p<0.05) in lead-exposed workers. The relationship between biomarkers of lead exposure/effect and HFC percentage was higher than the relationship between biomarkers of lead exposure/effect and SCE frequency. Accordingly, HFC analysis seemed to be more sensitive than the SCE analysis as a cytogenetic biomarker for lead exposure. Additionally, the statistically significant correlation (r2=0.880, p<0.01) between U-ALA excretion and HFC percentage in lead-exposed workers supported the probability of ALA mediated indirect mechanism for lead genotoxicity.

Urinary excretion of lead and δ-aminolevulinic acid in workers occupationally exposed to tetraethyl lead

Forty-nine refinery workers and 50 motor mechanics were selected and examined for total lead (PbT), inorganic lead (PbI), and δ-aminolevulinic acid (ALA) in urine. The worker groups were exposed to tetraethyl lead (TEL) mainly by inhalation, but motor mechanics received additional exposure by skin because of hand cleansing with gasoline.The levels of urinary ALA (ALA-U) and urinary PbT (PbT-U) in refinery workers and motor mechanics were found to be significantly higher than the control group (p<0.05). The correlation between the ALA-U and PbT-U was found significant in both worker groups (p<0.001); however, relatively higher positive correlation was found between ALA-U and urinary inorganic lead (PbI-U) in TEL-exposed workers.

Synthesis and In Vitro Activity of Polyhalogenated 2-phenylbenzimidazoles as a New Class of anti-MRSA and Anti-VRE Agents.

A series of novel polyhalogenated 2‐phenylbenzimidazoles have been synthesized and evaluated for in vitro antistaphylococcal activity against drug‐resistant bacterial strains (methicillin‐resistant Staphylococcus aureus, and vancomycin‐resistant Enterococcus faecium. Certain compounds inhibit bacterial growth perfectly. 11 was active than vancomycin (0.78 μg/mL) with the lowest MIC values with 0.19 μg/mL against methicillin‐resistant Staphylococcus aureus, 8 and 35 exhibited best inhibitory activity against vancomycin‐resistant Enterococcus faecium (1.56 μg/mL). The mechanism of action for this class of compounds appears to be different than clinically used antibiotics. These polyhalogenated benzimidazoles have potential for further investigation as a new class of potent anti‐methicillin‐resistant Staphylococcus aureus and anti‐vancomycin‐resistant Enterococcus faecium agents.