Eren Ozcagli

Mercury Exposure in Dental Practice

Since elemental mercury is absorbed by dental professionals through direct skin contact or inhalation, the use of mercury in dental amalgam continues to be a controversial issue. In this study, the authors address the possible health risk of occupational exposure to mercury vapor in the dental office. The cytogenetic examination of leukocytes with alkaline comet assay and blood mercury levels with Atomic Absorption Spectrometer of dentists exposed to mercury vapor below 0.1mg/m(3) concentrations failed to find cytogenetic damage and related correlation. However, higher cytogenetic damage and blood mercury levels evaluated in controls from mercury intake by seafood consumption justifies additional study.

Molecular biomarkers of oxidative stress and role of dietary factors in gasoline station attendants

Exposure to benzene promotes oxidative stress through the production of ROS, which can damage biological structures with the formation of new metabolites which can be used as markers of oxidant/antioxidant imbalance. This study aims to assess modifications in circulating levels of advanced oxidation protein products (AOPP), advanced glycation end-products (AGE) and serum reactive oxygen metabolites (ROMs) in a group of gasoline station attendants exposed to low-dose benzene and to evaluate the influence of antioxidant food intake on these biomarkers of oxidative stress. The diet adopted by the population examined consisted of compounds belonging to the classes of terpenoids, stilbenes and flavonoids, notably resveratrol, lycopene and apigenin. Ninety one gasoline station attendants occupationally exposed to benzene and 63 unexposed male office workers were recruited for this study. Urinary trans, trans-muconic acid (t,t-MA) concentration, determined to assess individual exposure level, resulted significantly higher in exposed workers. In subjects exposed to benzene, we observed a significant increase (p < 0.001) in ROMs and AOPP levels, which were also negatively correlated with fruit and vegetables consumption. By contrast, AGE did not show a significant increase and consequently any relation with antioxidant food intake. Only ROMs, representing a global biomarker of oxidative status, resulted correlated to t,t-MA levels (p < 0.01), probably due to low-dose exposure. Increase of ROS induced by reactive benzene metabolites may promote specific biochemical pathways with a major production of AOPP, which seem to represent a more sensitive biochemical marker of oxidative stress in workers exposed to benzene compared to AGE. Furthermore, this is the first study demonstrating ROMs increment in subject exposed to benzene. These biomarkers may be useful for screening purposes in gasoline station workers and other subjects exposed to low-dose benzene. Moreover, a diet rich in fruits and vegetables demonstrated an inverse association with the levels of oxidative stress markers, suggesting a protective role of antioxidant food intake in workers exposed to oxidant agents.

Long-term exposure of rabbits to imidaclorpid as quantified in blood induces genotoxic effect.

The present in-vivo study focuses on the genotoxic effect of the neonicotinoid pesticide imidacloprid (IMI) in rabbits. The purpose of the study was to establish a possible relationship between exposure to the pesticide (dose and duration) and genotoxicity. Furthermore, an analytical method for the simultaneous determination of IMI and its major metabolite 6-chloronicotinic acid (6-ClNA) in blood was developed and validated. The isolation of the two analytes from blood was performed by liquid-liquid extraction with dichloromethane. Analysis was performed by Liquid Chromatography - Atmospheric Pressure Chemical Ionization - Mass Spectrometry (LC-APCI-MS). The method was applied on the determination of IMI and 6-ClNA in serum samples obtained from rabbits fed with the insecticide at two low doses. Furthermore, parameters of genotoxicity and cytotoxicity were evaluated by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the Cytokinesis Block Proliferation Index (CBPI), in lymphocytes of exposed rabbits. The results revealed a genotoxic effect of IMI for both exposed groups. There were statistically significant differences in the frequencies of BNMN and MN between control and exposed groups but there was no dose-dependence, neither time-dependence of the genotoxic effect for the administered doses. This is the first time that long term exposure to IMI in rabbits was studied for the determination of its genotoxic effect. The genotoxic effect of IMI as it is depicted by the current study is in accordance with previous studies.

Risk assessment for children exposed to DDT residues in various milk types from the Greek market.

The occurrence of residues of DDT and its metabolites was monitored in 196 cow milk samples of various pasteurized commercial types collected from the Greek market. Residue levels were determined by GC-MS analysis. In 97.4% of the samples at least one DDT isomer or one of the DDT metabolites was detected, in levels not exceeding the maximum permitted residue level by the EU. Hazard Index for both carcinogenic and non-carcinogenic effects was estimated under two assumptions: a) using DDT concentrations from positive samples and b) imputing LOD/2 as an arbitrary concentration for negative samples. No statistically significant differences in detected or summed residue (p > 0.05) concentrations between different milk types were observed, with the exception of specific metabolites of DDT in some milk types. Exposure assessment scenarios were developed for children aged 1, 3, 5, 7 and 12 years old based on estimated body weights and daily milk consumption. Hazard Indices for non-carcinogenic effects were below 0.109 covering also carcinogenic effects according to WHO approach. The cancer risk values for carcinogenic effects according to the US EPA Cancer Benchmark Concentration approach, ranged from 0.4 to 18. For both effects the highest values were calculated for the 1- to 3-year-old age groups.

Assessment of genotoxic damage in nurses occupationally exposed to anaesthetic gases or antineoplastic drugs by the comet assay.

The potential mutagenic/carcinogenic action of waste anaesthetic gases and antineoplastic drugs in occupationally exposed human populations has been previously reported in several studies. Antineoplastic agents discovered in the first two decades of cancer therapy (1950 to 1970) largely interact with DNA or precursors, inhibiting the synthesis of DNA or causing irreparable damage to DNA itself. Considering the mechanisms of the antineoplastic drugs that are used, it is not surprising that many persons involved in health care, especially nurses, are worried about the health effects of these drugs. Experimental and epidemiological studies suggest that genotoxic effects can arise from inhalation anaesthetics. Due to their widespread use in operating rooms, there is a great concern that operating room personnel as well as patients might be at health risk from anaesthetics. The aim of the present study was to assess the possible genotoxic risk, by the alkaline comet assay, in the peripheral blood lymphocytes of nurses who are handling antineoplastic drugs or are exposed to waste anaesthetic gases.

Oxidative DNA damage and total antioxidant status in rats during experimental gram-negative sepsis

Sepsis and septic shock remains as leading cause of death in adult intensive care units. It is widely accepted that gram-negative bacteria and their endotoxins cause sepsis and septic shock, predominantly. Enhanced generation of reactive oxygen species may be responsible for tissue injury in septic shock and endotoxemia. The aim of this study was to assess oxidative DNA damage and the total antioxidant status (TAS) in peripheral lymphocytes of rats during different intraperitoneal gram-negative sepsis stages. Adult male Sprague-Dawley rats were divided randomly into four groups. Control group was intraperitoneally inoculated with 2 mL of pyrogene-free saline (Group I, n = 6), and the other rats received an intraperitoneal inoculum with 2 mL of saline containing 2 × 108 CFU of Escherichia coli. The animals were killed at time zero (Group I, n = 6), at 6th (Group II, n = 7), 12th (Group III, n = 7), and 24th (Group IV, n = 7) hour after the E. coli inoculation. Oxidative DNA damage in peripheral lymphocytes of rats was evaluated by modified comet assay (single-cell gel electrophoresis). Formamidopyrimidine DNA glycosylase (Fpg) and Endonuclease III (Endo III) were used to detect oxidized purines and pyrimidines, respectively. Total antioxidant quantification was carried out using ABTS+ (2,2′-Azino-di-[3 ethylbenzthiazoline sulphonate]) radical formation kinetics (Randox kit) in serum samples. Significant elevations of basal levels of strand breaks (SB) in Group IV were observed as compared with Group I, II, and III. There was a significant increase in Fpg sites in Group III as compared with Group I and II. However, there was no significant difference in terms of Endo III sites in any of the groups. Although the TAS was decreased with the stages of sepsis, this moderate decrease was significant in only Group IV as compared with Group I. There was no statistically significant correlation between DNA damage and TAS for any of the groups.

Cardiotoxicity in rabbits after long-term nandrolone decanoate administration

Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric acid-reactive species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period.

Assessment of Individual Susceptibility to Baseline DNA and Cytogenetic Damage in a Healthy Turkish Population: Evaluation with Lifestyle Factors

BACKGROUND Cytogenetic biomarkers are most frequently used well-established endpoints in human population studies with their sensitivity for measuring exposure to genotoxic agents. They have an important role as early predictors of cancer risk. Identification of individual genotypes of metabolic gene polymorphisms helps to understand the modulation of cancer susceptibility by environmental exposures, such as cigarette smoking and other lifestyle factors. AIM To evaluate individual susceptibility to chemicals, we determined individual DNA damage related to glutathione S-transferase (GST) genotypes (GSTM1, GSTT1, and GSTP1) in a Turkish population. METHODS Peripheral blood lymphocytes (PBL) and DNA samples of 127 subjects were analyzed for the presence of DNA damage, using single-cell gel electrophoresis (the Comet assay), and for cytogenetic parameters (chromosomal aberrations [CAs], bleomycin-induced CA, and a cytokinesis-blocked micronucleus assay), and the polymerase chain reaction/restriction fragment length polymorphism method, respectively. RESULTS Individuals carrying a GSTT1-null allele showed higher frequencies of CA and micronucleus (MN) (p=0.026, p=0.003, respectively), whereas the GSTM1-null and GSTP1 mutant genotypes did not show any differences in cytogenetic parameters. Our findings demonstrated that none of the lifestyle factors (smoking, alcohol drinking, dietary habits, vitamin intake, and physical activity), except for vitamin intake (p=0.002), were significantly associated with the studied cytogenetic parameters. CONCLUSION Our results suggest that the GSTT1 gene polymorphism may influence the baseline cytogenetic frequency in a healthy population.

Antioxidant, Antimicrobial, Cytotoxic and Anticholinesterase Activities of SevenMushroom Species with their Phenolic Acid Composition

The study focused to evaluate cytotoxic, antioxidant, antimicrobial and anticholinesterase activities of methanol extracts of Pleurotus ostreatus Jacq. (Pleurotaceae), Boletus edulis Bull. (Boletaceae), Tricholoma populinum J. (Tricholomataceae) Helvella queletii Bres. (Helvellaceae), Armillaria tabescens Emel. (Physalacriaceae), Psathyrella candolleana Fr. (Psathyrellaceae) and Helvella leucopus Pers. (Helvellaceae) mushroom species. Phenolic acid profiles of these mushrooms were also determined to obtain further information on the correlation between the contents of phenolic compounds and studied activities. Cytotoxic activity of mushrooms was screened by MTT cytotoxicity assay on cancer (HeLa) and normal epithelium (NRK-52E) cell lines. To determine antioxidant potential of mushroom extracts free radical scavenging, reducing power, superoxide anion radical scavenging, total antioxidant and metal chelating activities were studied, To indicate anthicholinesterase activity the acetyl-and butyrylcholinesterase inhibitory activities of the mushroom extracts were studied. For antimicrobial activity disc diffusion method was applied. Phenolic profile of mushrooms were determined by HPLC system. The IC50 values of the extracts were 1.58-25.11 and 2.05-22.32 mg/mL for HeLa and NRK-52E cells, respectively. At antimicrobial activity the inhibiton zones were found to be as 1 ± 0.12-13 ± 0.23 mm. P. ostreatus, B. edulis and H. leucopus extracts were showed higher activities than the other mushroms at antioxidant, antimicrobial, anticholinesterase and cytotoxic activity.

Determination of DNA damage and telomerase activity in stanozolol-treated rats

Anabolic androgenic steroids (AAS) are performance-enhancing drugs commonly abused by atheletes. Stanozolol is a synthetic testosterone-derived anabolic steroid. Although it is well known that AAS have several side-effects, there are only few toxicological studies available on the toxic effects and mechanisms of action of stanozolol. The aim of this study was to investigate the genotoxic effects of stanozolol and to determine its effects on telomerase activity in Sprague-Dawley male rats. For this purpose, 34 male rats were divided into 5 groups as follows: i) the control group (n=5); ii) the propylene glycol (PG)-treated group (n=5); iii) the stanozolol-treated group (n=8); iv) the PG-treated group subjected to exercise (n=8); and v) the stanozolol-treated group subjected to exercise (n=8). PG is used as a solvent control in our study. Stanozolol (5 mg/kg) and PG (1 ml/kg) were injected subcutaneously 5 days/week for 28 days. After 28 days, the animals were sacrificed, and DNA damage evaluation (comet assay) and telomerase activity assays were then performed using peripheral blood mononuclear cells (PBMCs). Telomerase activity was measured by using the TeloTAGGG Telomerase PCR ELISA PLUS kit. The results of this study revealed that stanozolol treatment induced DNA damage, while exercise exerted a protective effect. Stanozolol treatment without exercise stimulation was associated with a significant increase in telomerase activity in the PBMCs.