The association between the OPRM1 A118G polymorphism and addiction in a Turkish population.

Susceptibility to addiction has a complex genetic basis that includes genes associated with the action and metabolism of drugs of abuse. One important gene in that respect is OPRM1, which codes for the µ-opioid receptor and has an important role in mediating the rewarding effects of addiction substances. The aim of our study was to assess the prevalence of the OPRM1 A118G polymorphism (rs1799971) in Turkish population and to investigate its association with opioid and other substance addiction. In addition, we examined the association of rs1799971 in addicted patients who were also diagnosed with psychiatric disorders. The study included 103 patients addicted to opioids, cocaine, ecstasy, alcohol, lysergic acid diethylamide (LSD), cannabis, and sedative/hypnotic substances and 83 healthy volunteers with similar demographic features as controls. rs1799971 polymorphisms were identified with the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). The genotype frequencies were significantly higher in the addicted patients than controls (32.0 % vs 16.9 %, respectively; p=0.027). The prevalence of the G allele was 16.1 % in the addicted group and 8.4 % in the control group (p=0.031). Our study confirmed the association between the rs1799971(G) allele frequency and opioid and other substance addiction, but not with psychiatric disorders.

The Relationship Between Glutathione S-Transferase-P1 and Beta-2 Adrenoreceptor Genotypes with Asthmatic Patients in the Turkish Population.

BACKGROUND: Individual differences in the activity of enzymes that metabolize xenobiotics can impact health and disease. Beta-2 adrenoreceptor (ADRB2) is a functional G-coupled protein expressed in the vascular endothelium of lungs, alveolar walls, and the ganglions of cholinergic nerves which induces bronchodilation in response to catecholamines. Glutathione S-Transferase-P1 (GSTP1) is a candidate pi class GST gene, which controls pi class glutathione S-transferase activity. AIMS: In this study we determined the relationship between the ADRB2 Arg16Gly polymorphism and GSTP1 polymorphisms, involved in bronchodilator response and oxidative stress, respectively, with susceptibility to asthma. METHODS: In this study, 129 asthmatic patients and 127 healthy control cases were recruited to determine ADRB2 and GSTP1 genotypes by allele-specific polymerase chain reaction and restriction fragment length polymorphism assays, respectively. RESULTS: The ADRB2 genotype frequencies of the patients and control cases were found to be 10.9% (Arg16Arg), 48.8% (Arg16Gly), and 40.3% (Gly16Gly) and 24.4% (Arg16Arg), 36.2% (Arg16Gly), and 39.4% (Gly16Gly), respectively. GSTP1 genotype frequencies of patients and control cases were found to be 55% (Ile105Ile), 43.4% (Ile105Val), and 1.6% (Val105Val) and 75.6% (Ile105Ile), 22% (Ile105Val), and 2.4% (Val105Val), respectively. In the case of the GSTP1 gene, we found statistically significant differences in the genotype frequency of Ile105Val and the allele frequency of Val105 in the asthmatic group compared with the controls. Moreover, we observed a relationship between allele frequencies and clinical phenotypes including atopia nocturnal dyspnea, and steroid dependency in the asthmatic patients. CONCLUSION: Our results suggest that the GSTP1 Ile105Val polymorphism may be linked to the severeness of airway dysfunction.

Helicobacter pylori and serum kynurenine-tryptophan ratio in patients with colorectal cancer.

AIM: To evaluate how Helicobacter pylori (H. pylori) is able to evade the immune response and whether it enhances systemic immune tolerance against colorectal cancer. METHODS: This prospective randomized study involved 97 consecutive colorectal cancer patients and 108 cancer-free patients with extra-digestive diseases. Colorectal cancer and cancer-free patients were assigned into subgroups according to H. pylori IgG seropositivity. Exposure to H. pylori was determined by IgG seropositivity which was detected by enzyme linked immunoassay (ELISA). Serum neopterin levels were measured by ELISA. Serum tryptophan, kynurenine, and urinary biopterin concentrations were measured by high performance liquid chromatography. Serum nitrite levels were detected spectrophotometrically. Serum indoleamine 2,3-dioxygenase activity was estimated by the kynurenine to tryptophan ratio and by assessing the correlation between serum neopterin concentrations and the kynurenine to tryptophan ratio. The frequencies of increased serum kynurenine to tryptophan ratio of H. pylori seronegative and seropositive colorectal cancer subgroups were estimated by comparing them with the average kynurenine to tryptophan ratio of H. pylori seronegative tumor-free patients. RESULTS: Compared with respective controls, in both H. pylori seronegative and seropositive colorectal cancer patients, while serum tryptophan levels were decreased (controls vs patients; seronegative: 20.37 ± 0.89 µmol/L vs 15.71 ± 1.16 µmol/L, P < 0.05; seropositive: 20.71 ± 0.81 µmol/L vs 14.97 ± 0.79 µmol/L, P < 0.01) the kynurenine to tryptophan ratio was significantly increased (controls vs patients; seronegative: 52.85 ± 11.85 µmol/mmol vs 78.91 ± 8.68 µmol/mmol, P < 0.01, seropositive: 47.31 ± 5.93 µmol/mmol vs 109.65 ± 11.50 µmol/mmol, P < 0.01). Neopterin concentrations in cancer patients were significantly elevated compared with controls (P < 0.05). There was a significant correlation between serum neopterin levels and kynurenine/tryptophan in control and colorectal cancer patients groups (rs = 0.494, P = 0.0001 and rs = 0.293, P = 0.004, respectively). Serum nitrite levels of H. pylori seropositive cancer cases were significantly decreased compared with seropositive controls (controls vs patients; 26.04 ± 2.39 µmol/L vs 20.41 ± 1.48 µmol/L, P < 0.05) The decrease in the nitrite levels of H. pylori seropositive cancer patients may be attributed to excessive formation of peroxynitrite and other reactive nitrogen species. CONCLUSION: A significantly high kynurenine/tryptophan suggested that H. pylori may support the immune tolerance leading to cancer development, even without an apparent upper gastrointestinal tract disease.

The role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: a case-control study in a Turkish population.

The aim of the present study was to investigate the role of some polymorphisms in GSTs (GSTM1, GSTT1 and GSTP1) which are very important protective mechanisms against oxidative stress and in OGG1 gene which is important in DNA repair, against the risk of type 2 diabetes mellitus (T2DM). 127 T2DM and 127 control subjects were included in the study. DNA was extracted from whole blood. Analyses of GSTM1 and GSTT1 gene polymorphisms were performed by allele specific PCR and those of GSTP1 Ile105Val and OGG1 Ser326Cys by PCR-RFLP. Our data showed that GSTM1 null genotype frequency had a 2-6 times statistically significant increase in a patient group (OR=3.841, 95% CI=2.280-6.469, p<0.001) but no significance with GSTT1 null/positive and GSTP1 Ile105Val genotypes was observed. When T2DM patients with OGG1 Ser326Cys polymorphism were compared with patients with a wild genotype, a 2-3 times statistically significant increase has been observed (OR 1.858, 95% CI=1.099-3.141, p=0.021). The combined effect of GSTM1 null and OGG1 variant genotype frequencies has shown to be statistically significant. Similarly, the risk of T2DM was statistically increased with GSTM1 null (OR=3.841, 95% CI=2.28-6.469), GSTT1 null+GSTP1 (H+M) (OR=4.118, 95% CI=1.327-12.778) and GSTM1 null+OGG1 (H+M) (OR=3.322, 95% CI=1.898-5.816) and GSTT1 null+OGG1 (H+M) (OR=2.179, 95% CI=1.083-4.386) as compared to the control group. According to our study results, it has been observed that the combined evaluation of GSTM1-GSTT1-GSTP1 and OGG1 Ser326Cys gene polymorphisms can be used as candidate genes in the etiology of T2DM, especially in the development of T2DM.

Association between XRCC1 ARG399GLN and P53 ARG72PRO polymorphisms and the risk of gastric and colorectal cancer in Turkish population.

Gastric cancer is one of the most common cancers of the gastrointestinal system, and its overall five-year survival rate is still 15 % to 20 %, as it can mostly be diagnosed at an advanced stage. On the other hand, although colorectal cancer has a rather good prognosis, mortality is one half that of the incidence.As carcinogenesis is believed to involve reactive radicals that cause DNA adduct formation, impaired repair activity, and weakened tumour suppression, it would help to understand the role of the polymorphisms of nucleotide excision repair enzyme XRCC1 and of tumour suppressor gene p53 in gastric and colorectal cancers. Our study included 94 gastric cancer patients, 96 colorectal cancer patients, and 108 cancer-free individuals as control with the aim to see if there was an association between XRCC1 Arg399Gln and p53 Arg72Pro polymorphisms and cancer susceptibility. DNA was extracted from peripheral blood cells and genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism. Polymorphism p53 Arg72Pro was not associated with either gastric or colorectal carcinoma, while XRCC1 Arg399Gln was not associated with the increased risk of colorectal cancer. However, XRCC1 homozygous Gln allele at codon 399 was associated with 2.54 times higher risk of gastric cancer.

DNA repair enzyme polymorphisms and oxidative stress in a Turkish population with gastric carcinoma.

Although the developmental stages of gastric carcinoma are still not clear, the constantly generated reactive oxygen and nitrogen species (ROS/RNS) may contribute to the process of carcinogenesis by interacting with DNA. 8-oxoguanine DNA glycosylase-1 (OGG1) is an enzyme involved in base excision repair of 8-oxoguanine that is one of the premutagenic lesions generated by ROS in DNA. The bulky adducts, are recognized and repaired by nucleotid excision repair (NER) enzymes, including xeroderma pigmentosum C and D (XPC, XPD). Eligible 106 gastric cancer patients and 116 cancer-free individuals constituted the study and control groups, respectively. Association between OGG1 Ser326Cys, XPC Lys939Gln, XPD Lys751Gln polymorphisms and the susceptibility tho cancer and the oxidative stress status were evaluated. DNA was extracted from peripheral blood cells and genotypes were determined by using PCR-RFLP. Serum nitric oxide, albumin concentrations, total antioxidant status and Helicobacter pylori IgG were determined. Serum albumin and nitric oxide of cancer patients were lower than that of the controls (P < 0.05). None of the evaluated polymorphisms or Helicobacter pylori IgG seropositivity associated with increased risk of gastric cancer, despite of the increased oxidative stress in cancer patients.

DNA damage, glutathione, and total antioxidant capacity in anesthesia nurses.

The possibilities of a potential mutagenic/carcinogenic action of waste anesthetic gases in occupationally exposed anesthesia personnel have been previously reported in several studies. The aim of this study was to assess the DNA damage, reduced glutathione (GSH), and total antioxidant capacity (TAC) in anesthesia nurses. DNA damage was determined with comet assay, GSH levels were measured spectrophotometrically, and TAC was determined by using Randox kit. Anesthesia nurses (n = 40) showed increased DNA damage in terms of mean percentage of the total DNA in the comet tail compared to controls (n = 40) (p < .001). Mean TAC and GSH levels of the anesthesia nurses were significantly lower than that of the controls (p < .001, p < .05, respectively). The results of this study indicate that occupational exposure to anesthetic gases induce DNA damage, which may lead to changes in TAC and GSH levels.

Oxidative stress, Helicobacter pylori, and OGG1 Ser326Cys, XPC Lys939Gln, and XPD Lys751Gln polymorphisms in a Turkish population with colorectal carcinoma.

The contribution of polymorphisms of DNA repair genes OGG1 Ser326Cys, XPC Lys939Gln, and XPD Lys751Gln in developing colorectal carcinoma is controversial. Whether the group 1A carcinogen Helicobacter pylori is a risk factor or not in these patients could not be clearly elucidated. One hundred ten colorectal cancer patients and 116 cancer-free individuals constituted the test and control groups, respectively. The association of OGG1 Ser326Cys, XPC Lys939Gln, and XPD Lys751Gln polymorphisms and the susceptibility to colorectal carcinoma with or without oxidative stress were evaluated. DNA was extracted from peripheral blood cells and genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. For serum nitric oxide and total antioxidant status assay, spectrophotometric analyses were used. Serum albumin measurements were performed using an autoanalyzer. H. pylori IgG was measured by ELISA. The serum albumin concentrations of cancer patients were significantly lower than those of the controls (p < 0.05). The carriers of the variant genotype of OGG1 (odds ratio: 0.963; 95% confidence interval: 0.446-2.079), XPC (0.789, 0.366-1.700), or XPD (0.532, 0.259-1.094) did not associate with the increased risk of cancer progression, despite the increased oxidative stress in cancer patients. Seropositivity of H. pylori IgG has been found to increase the risk of colorectal carcinoma by 2.2-fold.

The role of oxidative DNA damage, DNA repair, GSTM1, SOD2 and OGG1 polymorphisms in individual susceptibility to Barrett's esophagus.

Determination of the genetic alterations, which play a role in the etiology of Barrett's esophagus (BE), could help identify high-risk individuals for esophageal adenocarcinoma (EA). The aim of the present study was to investigate the role of oxidative DNA damage, glutathione (GSH) concentration as oxidative stress parameters and DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1 Ser326Cys genetic polymorphisms as individual susceptibility parameters in the etiology of BE. The study groups comprised BE patients who were clinically diagnosed (n = 40) and a healthy control group (n = 40). Basal DNA damage, pyrimidine and purine base damage after H(2)O(2) induction, H( 2)O(2) sensitivity, DNA repair capacity, oxidized pyrimidine and purine base damage repair were evaluated in peripheral blood lymphocytes with a modified comet assay using specific endonucleases (Endo III and Fpg). Polymerase chain reaction-restriction length polymorphism (PCR-RFLP)-based assays were used for genotyping. The patient group showed elevated levels of basal DNA damage, pyrimidine base damage and H(2)O(2) sensitivity as compared to controls (p < .05). DNA repair capacity, oxidized pyrimidine and purine base damage repair capacity, were not statistically different between patients and controls. GSH concentration was found to be significantly lower in smoking patients than in the controls (p < .05). None of the genetic variations changed the risk of having BE disease. However, patients carrying the variant OGG1 Cys allele showed elevated levels of pyrimidine base damage as compared to patients carrying the wild-type OGG1 Ser (p < .05). The results of this study point to a role of oxidative DNA damage in BE. However, DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1 Ser326Cys genetic polymorphisms appeared to play no role in the individual susceptibility to this disease.

The association of OGG1 Ser326Cys polymorphism and urinary 8-OHdG levels with lung cancer susceptibility: a hospital-based case-control study in Turkey.

High incidence and poor prognosis of lung cancer make it a major health problem worldwide. Although smoking is a major cause of lung cancer, only some smokers develop lung cancer, which suggests that there is a genetic predisposition in some individuals. 8-OHG is an important oxidative base lesion and may elevate due to cancer and smoking. It is repaired by 8-hydroxyguanine DNA glycosylase 1 (OGG1), which has several polymorphisms. Although the Ser326Cys polymorphism is consistently associated with a range of cancers, findings about this polymorphism and lung cancer risk are contradictory. To date, no study has examined this association in the Turkish population. We conducted a case-control study to investigate the association between OGG1 Ser326Cys polymorphism and the risk of lung cancer using PCR-RFLP. We also evaluated gene-smoking interaction and excretion of urinary 8-OHdG. Our results suggest that the OGG1 Ser326Cys polymorphism is not a genetic risk factor for lung cancer, and that the heterozygous genotype is associated with a significantly reduced risk for lung cancer. The levels of 8-OHdG did not correlate with the polymorphism and smoking. Larger association studies are needed to validate our findings, and mechanistic studies are needed to elucidate the underlying molecular mechanisms of this association.

Vth International Conference on Environmental Mutagens in Human Populations: introduction.

The Vth International Conference on Environmental Mutagens in Human Populations (VthICEMHP), 20-24 May 2007 was successfully completed in Antalya, Turkey. With approximately 200 participants from 35 countries, the conference participants enjoyed extensive exchange of scientific and cultural expertise. Like the previous conferences in this series, collaborative and sustainable projects were developed among the participants. Publications in this monograph represent outstanding reviews and experimental data from invited speakers.

Assessment of abnormal DNA repair responses and genotoxic effects in lead exposed workers.

BACKGROUND: One of the main sources of occupational exposure to lead (Pb) in Turkey is in workers of battery industries. Genotoxic studies in human populations exposed to this metal have had conflicting results. METHODS: Genotoxic effects of Pb were studied in blood cell samples from workers of battery manufactures exposed to Pb compounds by chromosomal aberration (CA) assay and X-ray induced challenge (XRC) assay to assess DNA damage and interference with DNA repair processes after an in vitro exposure of X-ray (1 Gy). The battery manufacturers (n=23) and 23 people who were not occupationally exposed to lead compounds were selected as a control group and classified into categories according to their blood lead levels. RESULTS: The CA frequencies in the exposed and control group were not significantly different (P>0.05) by conventional CA (CCA) assay, however, the XRC assay demonstrated significantly elevated CAs (P<0.05). Statistically non-significant but reduced DNA repair responses have also been observed in lead exposed workers. CONCLUSION: The results of this study showed significant increases in the CAs by XRC assay in Pb exposed workers compared to CCA assay. Our data suggests that Pb exposure may cause reduction in DNA repair capacity and these individuals will be more prone to DNA damage. Therefore, preventive measures should be improved against genotoxic risk in workplaces.

Polymorphisms related to estrogen and xenobiotic metabolism in healthy Turkish women.

BACKGROUND: Polymorphisms which are inherited alterations in the activity of cytochrome P450 1B1 (CYP1B1), catechol O-methyltransferase (COMT), manganese superoxide dismutase (MnSOD) hold the potential to define differences in estrogen metabolism and, thereby, possibly explain inter-individual differences in cancer susceptibility associated with estrogen-mediated carcinogenesis. METHODS: The CYP1B1 (L432V), COMT (V158M), MnSOD (Ala-9Val) genotypes, to examine estrogen metabolism and the influence of age of menarche/menopause, were determined by using different polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) based on genotyping assays. RESULTS: Women who carried CYP1B1 *3 and COMT-L alleles had an earlier age at menarche than the women who carried wild alleles (chi2 = 4.57, p = 0.032), whereas I did not observe any correlation in women with all mutant alleles. Also, CYP1B1 *3 and COMT-H genotypes were common among postmenopausal women with a body mass index (BMI) > 27 kg/m2 (Fisher exact test, p = 0.044). CONCLUSIONS: To my knowledge, this is the first genetic study on the association of these genes with susceptibility in Turkish women. Although the small sample size of each combination of estrogen metabolizing, results suggest that the CYP1B1 *3 and COMT-L alleles influence age at menarche in healthy Turkish women.

Genetic polymorphism of manganese superoxide dismutase (MnSOD) and breast cancer susceptibility.

Within mitochondria, manganese superoxide dismutase (MnSOD) provides a major defence against oxidative damage by reactive oxygen species (ROS). An alanine-9valine (Ala-9Val) polymorphism in the mitochondrial targeting sequence of MnSOD has been described and has recently been associated with risk of human breast cancer. Our present case-control study was performed to explore the association between MnSOD genetic polymorphism and individual susceptibility to breast cancer. Ala-9Val polymorphism in the signal sequence of the protein for MnSOD was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a study population. There was no significant difference in risk for breast cancer development between patients positive and negative for the MnSOD Ala allele with adjusted odds ratio (OR): 0.86 (95% confidence interval (CI(0.43 to 1.72). When MnSOD Ala was combined with either cytochrome P450 1B1 CYP1B1*1 and catechol O-methyltransferase COMT-L (V158M) genotypes, the risk for developing breast cancer was significantly increased in patients with a body mass index (BMI) greater than 24 kg m(-2) (OR: 1.42 (95%CI=1.04-1.93)).

Lack of association between RNASEL Arg462Gln variant and the risk of breast cancer.

BACKGROUND: The RNASEL G1385A variant was recently found to be implicated in the development of prostate cancer. Considering the function of RNase L and the pleiotropic effects of mutations associated with cancer, we sought to investigate whether the RNASEL G1385A variant is a risk factor for breast cancer. PATIENTS AND METHODS: A total of 453 breast cancer patients and 382 age- and sex-matched controls from Greece and Turkey were analyzed. Genotyping for the RNASEL G1385A variant was performed using an Amplification Refractory Mutation System (ARMS). RESULTS: Statistical evaluation of the RNASEL G1385A genotype distribution among breast cancer patients and controls revealed no significant association between the presence of the risk genotype and the occurrence of breast cancer. CONCLUSION: Although an increasing number of studies report an association between the RNASEL G1385A variant and prostate cancer risk; this variant does not appear to be implicated in the development of breast cancer.

N-acetyltransferase (NAT2) polymorphism and breast cancer susceptibility: a lack of association in a case-control study of Turkish population.

Increased exposure to environmental carcinogens, including several aromatic and heterocyclic amines (HAs), is suspected to be one factor contributing to incidence of breast cancer. The N-acetyltransferase 2 (NAT2) acetylation polymorphism have been associated with a number of drug-induced toxicities and cancer in various tissues, resulting from decreased capacity to activate/deactivate several aromatic amine, hydrazine drugs, as well as HA carcinogens. Ethnic differences exist in NAT2 genotype frequencies, which maybe a factor in cancer incidence. Our present case-control study in Turkey was performed to explore the association between NAT2 genetic polymorphism and individual susceptibility to breast cancer. The NAT2 genotypes (*4, *12A, *5A, *5B, *5C, *6, *7) were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 84 breast cancer patients and 103 healthy controls, and 50% and 56.3%, respectively, were found to be slow acetylator genotypes. There was no significant difference in risk for breast cancer development among patients with rapid and slow acetylators, with adjusted odds ratio 0.78 (95% confidence interval 0.44 to 1.38). Also, risk was not affected by different variables. To our knowledge, this is the first genetic study on the association of NAT2 genotypes with breast cancer in the TUrkish population, and this finding showed that NAT2 polymorphism does not play an important role in breast cancer risk of Turkish women by altering the capacity in deactivation of environmental carcinogens, even though small sample size and wide confidence interval.

Assessment of cytogenetic aberrations and comet assay in colorectal adenocarcinomas.

UNLABELLED: AIMS, BACKGROUND AND STUDY DESIGN: Few studies have investigated the karyotypes of colorectal carcinomas with emphasis on the correlation between cytogenetic findings and clinicopathologic features. The aim of our study involving 20 colorectal adenocarcinomas was to determine their genomic alterations at the chromosomal level by correlating the cytogenetic findings with the extent of DNA damage and clinicopathologic parameters and to compare the results with those of healthy controls. RESULTS: Cytogenetic evaluation of patients and controls revealed 10 abnormal karyotypes in patients with adenocarcinomas located in the rectum, sigmoid and rectosigmoid regions. Four had numerical and six had structural abnormalities. CONCLUSIONS: Statistical analysis revealed a significant difference compared with controls (P <0.01). The karyotypes and the extent of DNA damage assessed by the comet assay were also significantly correlated with tumor stage (P <0.01) using the Kruskal-Wallis non-parametric test, while no statistical significance was observed in relation to patient age and smoking.

Cytochrome P450 CYP1B1 and catechol O-methyltransferase (COMT) genetic polymorphisms and breast cancer susceptibility in a Turkish population.

Epidemiological studies indicate that most risk factors for breast cancer are related to reproductive and hormonal factors. Estrogen has been proposed to trigger breast cancer development via an initiating mechanism involving its metabolite, catechol estrogen (CE). Because of the important role of cytochrome P450 1B1 ( CYP1B1) and catechol O-methyltransferase ( COMT) in mammary estrogen and carcinogen metabolism, we examined the CYP1B1 and COMT genes to determine whether genetic variations could account for inter-individual differences in breast cancer. In this case-control study, we determined CYP1B1 and COMT genotypes in 84 breast cancer patients and 103 healthy unrelated women controls from a Turkish population. In the case of CYP1B1, we genotyped CYP1B1*3 (L432 V) allele. We found that carriers of the CYP1B1*3 allele were more frequent among breast cancer patients with adjusted odds ratio (OR) for age, age at menarche, age at first full-term pregnancy, body mass index (BMI) and smoking status of 2.32 (95% confidence interval 1.26-4.25) associated with the allele. However, this allele appeared to be a significant factor for susceptibility only in patients with a BMI greater than 24 kg/m(2). Menopausal status did not appear to affect susceptibility. In the case of COMT, there was no significant difference in susceptibility for breast cancer development between patients with low activity COMT-L (V158 M) allele and high activity COMT-H allele, and susceptibility was not affected by menopausal status, BMI or CYP1B1 genotype. We conclude that the CYP1B1* 3 allele appears to be a factor for susceptibility to breast cancer in Turkish women especially those with a BMI greater than 24 kg/m(2).

Cytogenetic analysis of buccal cells from shoe-workers and pathology and anatomy laboratory workers exposed to n-hexane, toluene, methyl ethyl ketone and formaldehyde.

People employed in the shoe manufacture and repair industry are at an increased risk for cancer, the strongest evidence being for nasal cancer and leukaemia. A possible causal role for formaldehyde is likely for cancer of the buccal cavity and nasopharynx. Exfoliated buccal cells are good source of tissue for monitoring human exposure to inhaled and ingested occupational and environmental genotoxicants. To assess the cytogenetic damage related to occupational exposure to airborne chemicals during shoe-making and the processes in pathology and anatomy laboratories, the micronuclei (MN) count per 3000 cells was measured in buccal smears from shoe-workers (group I, n = 22) exposed to mainly n-hexane, toluene and methyl ethyl ketone (MEK) and from anatomy and pathology staff (group II, n = 28) exposed to formaldehyde (FA). Eighteen male university staff were used as controls. The mean time-weighted average (TWA) concentrations of n-hexane, toluene and MEK in 10 small shoe workshops were 58.07 p.p.m., 26.62 p.p.m. and 11.39 p.p.m., respectively. The measured air concentrations of FA in the breathing zone of the anatomy and pathology laboratory workers were between 2 and 4 p.p.m. Levels of 2,5-hexadione (2,5-HD) and hippuric acid (HA), metabolic markers of n-hexane and toluene exposure, respectively, were significantly higher in the urine of workers in group I than in control subjects (p < 0.001 and p < 0.01, respectively). The mean (+/- SD) MN (0/00) [corrected] frequencies in buccal mucosa cells from workers in group I, group II and controls were 0.62 +/- 0.45%, 0.71 +/- 0.56% and 0.33 +/- 0.30%, respectively (p < 0.05 and p < 0.05 compared with controls for group I and group II, respectively). The effects of smoking, age and duration of exposure on the frequency of micronucleated buccal cells from workers in all three groups studied were also evaluated. Overall, the results suggest that occupational exposure to organic solvents, mainly n-hexane, toluene, MEK and FA, may cause cytogenetic damage in buccal cells and that use of exfoliated buccal cells seems to be appropriate to measure exposure to organic solvents.

Chromosomal damage in peripheral blood lymphocytes of traffic policemen and taxi drivers exposed to urban air pollution.

Urban air contains a diversity of chemical compounds, some of which are genotoxins. An increased risk of cancer has also been reported in occupations with heavy exposure to traffic-related pollution. The aim of this study was to assess the cytogenetic effects of urban air pollution by analyzing the chromosomal aberration (CA) frequencies in lymphocytes and to estimate the polycyclic aromatic hydrocarbons (PAHs) exposure by measuring urinary 1-hydroxypyrene (1-OHP) levels. A total of 15 traffic policemen and 17 taxi drivers working in the city of Ankara were the exposed groups and 23 healthy men working in the office departments were the control group. The overall mean +/- S.D. values of 1-OHP excretions of traffic policemen, taxi drivers and control subjects were 0.59 +/- 0.40 micromol/mol creatinine, 0.32 +/- 0.25 micromol/mol creatinine and 0.57 +/- 0.36 micromol/mol creatinine, respectively. Urinary 1-OHP levels of non-smoking policemen were significantly greater than those of nonsmoking control subjects (p < 0.05). The overall mean +/- S.D. values for CA frequencies (%) from policemen, taxi drivers and control group were 1.29 +/- 1.59, 1.81 +/- 1.79, and 0.26 +/- 0.73, respectively. There was a significantly greater frequency of CAs in exposed groups relative to the matched control population (p < 0.05; p < 0.01). Age, sex and smoking habits have not influenced the cytogenetic end-point in this study. Our results demonstrate that occupational exposure to urban air pollutants leads to a significant induction of cytogenetic damage in peripheral lymphocytes of traffic policemen and taxi drivers.