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Biomedical subjects

A E Karakaya

Publications and source records attributed to A E Karakaya.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of genotoxicity of sevoflurane and isoflurane in human lymphocytes studied in vivo using the comet assay.

In the present paper, we report data on the possible genotoxic properties of two inhalation anaesthetics--sevoflurane (SVF) and isoflurane (ISF) - in peripheral blood lymphocytes of patients before, during and after anaesthesia as compared to an unexposed control group. Both anaesthetics were evaluated for genotoxic activity using the comet assay. The exposed groups consisted of 24 ASA grades 1-2 unpremedicated patients (aged 20-66 years, anaesthetized 115-162 min for elective lower abdominal surgery), while the control group consisted of 12 healthy individuals. After induction of anaesthesia (thiopenthone sodium 5-7 mg/kg, fentanyl citrate 0.1mg and vecuronium bromide 0.1mg/kg), anaesthesia was maintained with inhalation of SVF 1-1.5% (n=12) or ISF 1-1.5% (n=12) in oxygen-air mixture. Venous blood samples were obtained before the induction of anaesthesia, at 60 and 120 min of anaesthesia and on the first, third and fifth days following anaesthesia. The comet assay detects DNA damage which includes strand breaks and alkaline labile sites induced directly by genotoxic agents as well as DNA degradation due to cell death. One hundred cells from each sample were examined and graded as no tailed, short and long tailed nuclei. The mean comet response was not different between controls and patients before anaesthesia. However, similar significant increases were observed in the mean comet response in blood sampled from patients at 60 (36.5+/-11.2, 37.8+/-12.1), or 120 min (53.1+/-17.1, 50.0+/-12.2) of anaesthesia and on the first day (37.8+/-15.1, 35.2+/-15.7) after anaesthesia in SVF and ISF treated groups, respectively. Removal of the DNA damage was observed after the third day of anaesthesia and the repair was completed within 5 days. The DNA damage detected in lymphocytes of patients during anaesthesia with SVF or ISF showed similar results as demonstrated by an increased mean comet migration at 120 min of anaesthesia and the cells were able to repair the induced DNA damage completely on the fifth postoperative day.

Adult↗
PubMed2001

Assessment of DNA strand breakage by comet assay in diabetic patients and the role of antioxidant supplementation.

Diabetes patients often show increased production of reactive oxidative species (ROS) together with vascular complications. The presence of these ROS may lead to increased DNA damage in peripheral blood lymphocytes that may be revealed by the comet assay. To test whether DNA is damaged in diabetes, peripheral blood samples were taken from 30 control individuals and 63 diabetic patients (15 insulin dependent (IDDM) and 48 non-insulin dependent (NIDDM)) and the alkaline comet assay was used to evaluate background levels of DNA damage. Significant differences were detected between control and diabetic patients in terms of frequencies of damaged cells. The extend of DNA migration was greater in NIDDM patients by comparison with IDDM patients which might indicate that IDDM patients are handling more oxidative damage on a regular basis. Smoker individuals had higher frequencies of cells with migration by comparison with the non-smokers in both groups. Also, clear differences between patients on placebo and on Vitamin E supplementation for 12 weeks were observed on the basis of the extend of DNA migration during single cell gel electrophoresis.

Adult↗
PubMed2001

Catechol-O-methyltransferase (COMT) genetic polymorphism in a Turkish population.

Catechol-O-methyltransferase (COMT) inactivates neurotransmitters, catechol hormones and drugs such as levodopa and methyldopa. A low activity allele has been demonstrated at codon 108/158 of the soluble and membrane-bound COMT, respectively, whereby a G to A transition results in a valine to methionine substitution. Ethnic and inter-individual differences in red blood cell COMT activity have been observed in the different populations studied so far. Since, no information is available on inter-individual variability of COMT genotype in Turkish population, we genotyped 217 healthy, unrelated Turkish individuals. The allelic frequencies of COMT gene in the Turkish population were found to be the same as has been observed in Caucasians, but different from Orientals.

Adult↗
PubMed2001

Determination of coumarin metabolism in Turkish population.

Cytochrome P450 2A6 is an important human hepatic P450 which activates precarcinogens and oxidizes some drug constituents such as coumarin, halothane, and the major nicotine C-oxidase. Genetic polymorphism exists in the CYP2A6 gene. CYP2A6*1 (wild type) is responsible for the 7-hydroxylation of coumarin. The point mutation (T to A) in codon 160 leads to a single amino acid substitution (Leu to His) and the resulting protein, CYP2A*2 is unable to 7-hydroxylate coumarin. Gene conversion in exons 3, 6, and 8 between the CYP2A6 and the CYP2A7 genes creates another variant, CYP2A6*3. In this study, healthy male and female Turkish volunteers (n = 50) were administered 2 mg coumarin, and urine samples were analyzed for their content of the coumarin metabolite, 7-hydroxycoumarin (7OHC), by high-performance liquid chromatography (HPLC). Genetic polymorphism for CYP2A6 was detected by using two-step polymerase chain reaction (PCR) to identify CYP2A6*1, CYP2A6*2, and CYP2A6*3 in 13 of these subjects. The percentage of the dose excreted of total 7OHC in relation to CYP2A6 genotype and excretion of nicotine/cotinine was also evaluated to demonstrate the role of CYP2A6 in nicotine metabolism. The majority of Turkish subjects (68%) excreted less than 60% of the 2-mg dose as coumarin metabolite. The allelic frequencies were detected as 0.88 for CYP2A6*1 allele; 0.12 for CYP2A6*3 allele in 13 individuals. No heterozygous and homozygous individuals were identified for the CYP2A6*2 allelic variant. Phenotyping and genotyping for drug metabolizing enzymes are of great importance in studies correlating precarcinogen activation or drug metabolism to the CYP2A6 genotype in smoking behavior when populations are investigated.

Adult↗
PubMed2001

Micronuclei frequencies in exfoliated nasal mucosa cells from pathology and anatomy laboratory workers exposed to formaldehyde.

Formaldehyde (FA) is a widely used industrial chemical. Sufficient evidence exists to consider FA as an animal carcinogen. A possible causal role for FA may be considered likely for cancer of the nasopharynx and the nasal cavities in humans. The frequency of micronuclei (MN) in cells of the nasal mucosa was evaluated for 23 individuals in pathology and anatomy laboratories exposed to FA. Twenty-five healthy subjects were selected from the university and hospital staff as a control group. The measured air concentrations of FA in the breathing zone of the laboratory workers were between 2 and 4 ppm. The mean +/- SD values of nasal mucosa MN (per 1000) frequency from exposed and controls were 1.01 +/- 0.62 and 0.61 +/- 0.27, respectively (p < 0.01). Effect of smoking, age, sex and duration of exposure on the genotoxicity parameters analyzed were also evaluated. Our data suggest that low level exposure to FA is associated with cytogenetic changes in epithelial cells of the nasal region and that nasal mucosa cells exposed through respiration is an important target of FA-induced genotoxic effects.

Adult↗
PubMed2000

Influence of GSTM1 genotype on comet assay and chromosome aberrations after induction by bleomycin in cultured human lymphocytes.

Investigators have demonstrated that the mutagen sensitivity assay, based on the quantification of bleomycin (BLM)-induced chromatid breaks in short-term cultured peripheral lymphocytes, can be a marker of cancer susceptibility. Although many factors can contribute to variability in human biomonitoring studies, genetic susceptibility (the influence of polymorphic metabolising genes on response to environmental mutagens) should be considered whenever appropriate. Glutathione-S-transferases (GSTs) encode a family of detoxifying phase II enzymes catalysing the conjugation of glutathione to electrophilic compounds. Studies on Caucasians indicate that about 45% of individuals lack the glutathione-S-transferase M1 (GSTM1, null) enzyme, and are therefore, theoretically at a higher risk to the toxic effects of chemicals. The aim of the present study was to investigate this hypothesis further by evaluating whether the GSTM1 genotype influences the background [corrected] level of DNA damage and the induction of chromosomal aberrations by BLM in peripheral-blood lymphocytes. The alkaline comet assay was used to evaluate background levels of DNA damage in unstimulated lymphocytes while standard cytogenetic techniques were used in mitogen-stimulated lymphocytes treated with BLM. Without BLM treatment, individuals with the GSTM1 null genotype had no significant difference in frequencies of damaged cells by comparison to individuals with the GSTM1 genotype. Also, no significant differences between the two groups of individuals (GSTM1 positive and GSTM1 null) were observed for BLM-induced chromosomal aberrations.

Adult↗
PubMed2000

Cigarette smoking, N-acetyltransferase 2 acetylation status, and bladder cancer risk: a case-series meta-analysis of a gene-environment interaction.

Tobacco use is an established cause of bladder cancer. The ability to detoxify aromatic amines, which are present in tobacco and are potent bladder carcinogens, is compromised in persons with the N-acetyltransferase 2 slow acetylation polymorphism. The relationship of cigarette smoking with bladder cancer risk therefore has been hypothesized to be stronger among slow acetylators. The few studies to formally explore such a possibility have produced inconsistent results, however. To assess this potential gene-environment interaction in as many bladder cancer studies as possible and to summarize results, we conducted a meta-analysis using data from 16 bladder cancer studies conducted in the general population (n = 1999 cases), Most had been conducted in European countries. Because control subjects were unavailable for a number of these studies, we used a case-series design, which can be used to assess multiplicative gene-environment interaction without inclusion of control subjects. A case-series interaction odds ratio (OR) > 1.0 indicates that the relationship of cigarette smoking and bladder cancer risk is stronger among slow acetylators as compared with rapid acetylators. We observed an interaction between smoking and N-acetyltransferase 2 slow acetylation (OR, 1.3; 95% confidence interval, 1.0-1.6) that was somewhat stronger when analyses were restricted to studies conducted in Europe (OR, 1.5; confidence interval, 1.1-1.9), a pooling that included nearly 80% of the collected data. Using the predominantly male European study population and assuming a 2.5-fold elevation in bladder cancer risk from smoking, we estimated that the population attributable risk percent was 35% for slow acetylators who had ever smoked and 13% for rapid acetylators who had ever smoked. These results suggest that the relationship of smoking and bladder cancer is stronger among slow acetylators than among rapid acetylators.

Acetylation↗
PubMed1999

Investigation of some immunological functions in a group of asphalt workers exposed to polycyclic aromatic hydrocarbons.

To investigate the effects of polycyclic aromatic hydrocarbons (PAHs) on the human immune system, analyses were performed on T-cell subsets (CD4+, CD8+), B-cells (CD19+), serum immunoglobulin levels (IgG, IgM, IgA) and white blood cell percentages of 16 male workers who were employed in road paving operations and compared to 12 unexposed male controls. PAH exposure was assessed using urinary 1-hydroxy-pyrene (1-OHP) levels and was found to be significantly higher in workers than in the controls. While the CD4+ cell percentage and the CD4+/CD8+ ratio were significantly higher in the PAH-exposed group, the percentages of CD8+ and CD19+ cells were unchanged. There was also a significant enhancement in serum IgG levels and the percentage of monocytes in the workers compared to the control group. These data suggest that chronic exposure to PAHs may affect some immune functions in humans.

Adult↗
PubMed1999

The micronucleus assay in exfoliated buccal cells: application to occupational exposure to polycyclic aromatic hydrocarbons.

Many polycyclic aromatic hydrocarbons (PAHs) have been identified as cancer-inducing chemicals for animals and/or humans. Also, there is sufficient evidence that exposures in the occupational settings are carcinogenic or probably carcinogenic to human. Engine exhaust and used engine oils are major PAH sources in engine repair workshops and traffic. Analysis of micronucleus (MN) in exfoliated buccal cells is a sensitive method for monitoring genetic damage in human populations. In our study, we used three different occupational groups (Group 1; engine repair workers, Group 2; taxi drivers, Group 3; traffic police) and two controls (Control I for Group 1 and Control II for Group 2 and Group 3) for the exposed groups. We analysed MN frequencies in exfoliated buccal cells and compared the exposed groups (Group 1; n=34, Group 2; n=17, Group 3; n=15) and subjects not occupationally exposed to PAH (Control I; n=28, Control II; n=20). The mean (+/-S.D.) MN (%) frequencies in exfoliated buccal cells from Group 1 and Control I were 0.07+/-0.05 and 0. 05+/-0.04, respectively (p>0.05; Table 2). The mean (+/-S.D.) MN (%) frequencies in exfoliated buccal cells from Group 2, 3 and Control II were 0.12+/-0.05, 0.10+/-0.05 and 0.03+/-0.03, respectively (p<0. 0001, p<0.05; Table 2) Smokers and nonsmokers do not differ with respect to the incidence of MN in all groups.

Adolescent↗
PubMed1999

Serum paraoxonase activity and phenotype distribution in Turkish subjects with coronary heart disease and its relationship to serum lipids and lipoproteins.

Recently, biochemical studies of paraoxonase in the serum of humans have shown that much of this enzymes' activity is associated with high-density lipoprotein (HDL) and paraoxonase may play a role in lipid metabolism preventing the accumulation of the lipoperoxides. In this study, a possible relationship between coronary heart disease (CHD) and paraoxonase activity were investigated. Serum triglycerides, total cholesterol, HDL-cholesterol and paraoxonase activity were measured in unrelated healthy donors and CHD patients. It was found that paraoxonase activity was trimodally distributed in both groups but no statistically significant difference was found between phenotype distributions of controls and CHD patients (gene frequencies; 0.632 and 0.382 of controls, 0.702 and 0.298 of patients for the A and B alleles, respectively). However, in CHD group, a high possibility was found to be phenotype A compared with the control group. A relative risk of 1.48 (95% confidence intervals (CI), 0.986-2.227) was found for the relation between CHD and the paraoxonase activity. Patients' HDL-cholesterol values were lower and triglycerides were higher than controls (P<0.001). It may be concluded from the present study that although no statistically significant difference was found between paraoxonase phenotype distributions of controls and CHD patients, a decrease in paraoxonase activity could become a risk factor for this disease.

Adult↗
PubMed1999

Effects of occupational chronic co-exposure to n-hexane, toluen, and methyl ethyl ketone on NK cell activity and some immunoregulatory cytokine levels in shoe workers.

1. To evaluate the effects of occupational long-term co-exposure to n-hexane, toluen, and methyl ethyl ketone (MEK) on NK cell activity and serum IL-2, gamma-IFN levels, we studied a group of workers employed in a shoe factory where the jobs include use of glues and adhesives containing mainly n-hexane, and at low concentrations, toluen and MEK. 2. No differences were found in these parameters even in those workers with 3.3-fold higher mean levels of urine, 2,5-Hxdn and approximately twofold higher mean levels of urine hippuric acid as compared to controls. 3. We conclude that chronic co-exposure to n-hexane, toluen, and MEK at these levels is not associated with an impairment on either NK cell activity or serum IL-2 and gamma-IFN levels.

Adolescent↗
PubMed1998

Cytogenetic biomonitoring of workers exposed to bitumen fumes.

Bitumen samples and fumes consist essentially of polycyclic hydrocarbons (PAH) and their derivatives, some of which are known to be carcinogenic or co-carcinogenic in animals. The level of total PAH is low when compared with coal-tar products. There is very limited data on possible health risk from exposure to bitumen fumes in workers. In this study, sister-chromatid exchange (SCE), micronuclei (MN) and high frequency of SCE cells (HFCs) were determined for 28 workers exposed to bitumen fumes and 28 control subjects. Urinary 1-hydroxypyrene (1-OHP) excretion was used as a biomarker of occupational exposure to PAH. The mean value of 1-OHP excretion of workers was 0.78+/-0.46 micromol/mol creatinine and for controls 0.52+/-0.44 micromol/mol creatinine (p<0.05). The mean values of SCE per cell and the frequency ( per thousand) of MN in peripheral lymphocytes from the workers and controls were 5.13+/-0. 64, 4.71+/-0.67, and 2.25+/-0.42, 1.79+/-0.32 respectively (p<0.05, p<0.0001). The mean value of HFCs for workers and controls were 7. 85+/-2.3 and 7.05+/-3.16, respectively (p>0.05). Our data reveal that bitumen fumes during road paving operations are absorbed by workers and that bitumen fume exposure is able to significantly induce cytogenetic damage in peripheral lymphocytes of workers after controlling some possible confounding factors, such as age, sex and smoking habits.

Adult↗
PubMed1998

Use of alkaline comet assay (single cell gel electrophoresis technique) to detect DNA damages in lymphocytes of operating room personnel occupationally exposed to anaesthetic gases.

Here, we report the possible in vivo induction DNA damage by exposure to various waste anaesthetic gases such as halothane, nitrous oxide and isoflurane. The alkaline comet assay (single cell gel electrophoresis technique) was carried out on 66 operating room personnel (anaesthetists [doctors]; anaesthesia nurses and anaesthesia unit technicians) currently employed at the Ankara Hospital in Turkey. A significant increase in the number of lymphocytes with DNA migration was observed in operating room personnel as compared to controls. Also, the extent of damage in exposed smokers were significantly higher than exposed nonsmokers. This study supports the existence of an association between DNA damage and occupational exposure to inhalation anaesthetics.

Adult↗
PubMed1998

DNA damage evaluated by the alkaline comet assay in lymphocytes of humans anaesthetized with isoflurane.

In the present paper, we report data on the possible DNA damage, induced in vivo by isoflurane using the alkaline single cell gel electrophoresis technique (SCGE-comet assay) in patients before/after anaesthesia and in control group. Twelve patients, aged 22-66 years old, were anaesthetized for elective abdominal surgery with isoflurane in oxygen for 120-162 min (mean: 133.2 min). Venous blood samples were obtained from the patients before the induction of anaesthesia, at 60 and 120 min of anaesthesia and on the first, third and fifth following days of anaesthesia. SCGE was examined in 100 cells from each specimen graded as undamaged, intermediate and tailed nuclei. The number of undamaged nucleus was almost same in control and in patients before anaesthesia. However, significant differences were observed in proportion of undamaged, intermediate and tailed nucleus of patients at 60 and 120 min of anaesthesia and on the first day. DNA damage started to return to normal rates after the third day of anaesthesia and were almost identical with the rates of control group five days later.

Adult↗
PubMed1998

Chromosomal aberrations and alkaline comet assay in families with habitual abortion.

Within the pathology of human reproduction, genetic abnormalities play an important role in spontaneous abortions. This paper describes the morphologic, karyotypic features of a consecutive series of singleton spontaneous abortions collected as part of this study and also reports the application of the alkaline comet assay to assess levels of DNA damage in 31 couples comprised of 13 control couples and a patient group of 18 couples with a history of more than one fetal loss. For the cytogenetic analyses, the conventional lymphocyte culture method was applied to all subjects. In this analysis, two women with habitual abortion were determined to carry balanced chromosomal translocation. The alkaline comet assay (single cell gel electrophoresis technique) was applied also to lymphocytes. The comparison of the results of alkaline comet assay in patient and control individuals showed a significant difference in the number of damaged cells. The cells were evaluated according to their grades of damage as: normal (undamaged-no migration), limited migration, (at low damage level) and extensive migration (comet imaged cells-with increasing numbers of breaks, DNA pieces migrate freely into the tail forming a comet image). The frequency of limited migrated and extensive migrated cells in the women in the patient group were higher than in the women in the control group (p<0.001). However, all above parameters were equal for husbands in both the control and patient group (p>0.05).

Abortion, Habitual↗
PubMed1998

Biological monitoring of young workers exposed to polycyclic aromatic hydrocarbons in engine repair workshops.

Several polycyclic aromatic hydrocarbons (PAHs) are carcinogenic in rodents, while exposure to these compounds has been associated with various types of human cancer. Engine exhaust and used engine oils are major PAH sources in engine repair workshops. Urinary 1-hydroxypyrene (1-OHP) levels and some genotoxicity parameters (sister-chromatid exchange, SCE; micronucleus, MN) have been compared among engine repair workers (n = 61, age: between 13 and 18) and workers not occupationally exposed to PAH (n = 30, age: between 13 and 19). The mean value (+/- S.E.) of urinary 1-OHP excretions of workers was 4.71 +/- 0.53 micromol/mol creatinine and also mean urinary 1-OHP for controls was found to be as 1.55 +/- 0.28 micromol/mol creatinine. The mean values (+/- S.E.) of SCE frequency per cell in peripheral lymphocytes from the workers and controls were 4.47 +/- 0.09 and 4.06 +/- 0.16, respectively (p < 0.05). The mean (+/- S.E.) MN (per thousand) frequencies in peripheral lymphocytes from the workers and controls were 1.87 +/- 0.04 and 1.56 +/- 0.06, respectively (p < 0.0001). The effect of smoking for the above parameters were also evaluated.

Adolescent↗