Evaluation of genotoxic effects in a group of workers exposed to low levels of styrene

Occupational exposure to styrene was studied in a group of workers engaged in the production of fiberglass-reinforced plastics. Sister-chromatid exchanges (SCE), micronuclei (MN), and DNA damage (evaluated by means of comet assay) were measured in peripheral blood cells from the exposed workers and from a control population. Mandelic acid concentration, an indicator of styrene exposure level, was measured in urine samples collected at the end of the work shift. Average estimated values for styrene exposure were slightly below the threshold limit value (TLV) of 20 ppm recommended by the American Conference of Governmental Industrial Hygienists. Significant increases (P< or =0.01) have been found for SCE and MN frequencies and comet tail length among exposed individuals, as well as significant decreases (P< or =0.01) in the proliferation indices, as compared with control population. High correlation has been obtained between endpoints evaluated and exposure length, and increased values of SCE and MN frequencies and comet tail length have been found among smokers only in the exposed population. The high correlation obtained among SCE and MN frequencies and comet tail length, and the increase of these parameters in the exposed group with regard to control group justify the use of these three biomarkers in the evaluation of genotoxic effects in human populations exposed to styrene.     

Cytogenetic analysis in lymphocytes from workers occupationally exposed to low levels of ionizing radiation

The aim of the present study was to perform a cytogenetic analysis in peripheral lymphocytes of 36 individuals occupationally exposed to low levels of ionizing radiation, and compare the results with 36 controls, using the chromosomal aberrations test (CA), sensitivity to bleomycin and cytokinesis-blocked micronucleus assay (MN). The frequencies of CA/100 cells observed for the exposed workers were not significantly higher than in controls (P>0.05). The mean break/cell (b/c) for the controls and exposed workers was 0.59±0.39 and 0.57±0.29, respectively (P>0.01). The MN frequencies were significantly increased (P<0.01) in exposed workers (6.13±3.18) in comparison with controls (5.11±3.85). The mean MN was also statistically higher in the non-smoker exposed when compared with non-smoker controls, 5.80±3.09 and 5.15±4.08, respectively (P<0.01). The cytogenetic analysis of MN proved to be the most sensitive biological marker to assess the cellular response to low levels of irradiation.     

Occupational exposure to styrene: modulation of cytogenetic damage and levels of urinary metabolites of styrene by polymorphisms in genes CYP2E1, EPHX1, GSTM1, GSTT1 and GSTP1

Styrene is widely used in the production of various plastics, synthetic rubber and resins. The aim of this study was to evaluate if individual polymorphisms in xenobiotic metabolizing enzymes, related with the metabolic fate of styrene, could modify individual susceptibility to the possible genotoxic effects of the styrene exposure. Twenty-eight reinforced plastic workers and 28 control subjects were studied. In the selected population the urinary styrene metabolites mandelic (MA) and phenylglyoxylic (PGA) acids were quantified, sister chromatid exchanges (SCE) and micronuclei (MN) were assessed in peripheral lymphocytes and all the subjects were genotyped for GSTM1, GSTT1 (gene deletions), GSTP1 (codon 105 ile==>val), EPHX1 (codons 113 tyr==>his and 139 his==>arg) and CYP2E1 (DraI polymorphism in intron 6). The results obtained showed a significant difference between the levels of SCE, but not in MN levels, in exposed workers as compared with the control group. The GSTP1 and CYP2E1 individual genotypes modulate the baseline levels of SCE that are lower in non-wild type individuals for both polymorphisms. The GSTM1 null individuals with low levels of exposure have significantly higher urinary levels of MA+PGA. The present data seem to suggest that apart from the methodology usually used for monitoring populations occupationally exposed to styrene (urinary metabolites and biomarkers of early biological effects) the analysis of individual genotypes associated with the metabolic fate of styrene should also be carried out in order to evaluate the individual genetic susceptibility of exposed populations.     

Genotoxicity study in lymphocytes of offset printing workers

The potential cytogenetic damage in offset printing workers was evaluated using sister chromatid exchanges (SCEs), chromosome aberrations (CAs) and micronuclei (MN) as biomarkers in peripheral lymphocytes of 26 volunteers (14 workers, 12 controls). The CA, SCE and MN frequency of offset printing workers was significantly higher than in their controls. The replication index (RI) was not affected while the mitotic index (MI) was affected most in the workers. It can be concluded from this study that chronic occupational exposure to printing dyes and thinner may lead to a slightly increased risk of genetic damage among offset printing workers.     

Assessment of micronuclei in lymphocytes from workers exposed to vapours and aerosols of bitumen

We investigated the micronucleus frequencies in peripheral blood lymphocytes of 225 mastic asphalt workers (age 17-62 years) and 69 non-bitumen-exposed road construction workers (age 18-64 years) in Germany before and after the working shift. Median shift exposure to vapours and aerosols of bitumen of exposed workers was 3.0 mg/m3. Micronuclei (MN) were determined with a standard method using cytochalasin B. Median MN frequency was 6.0 (interquartile range (IQR) 4.0-8.5) MN/1,000 binucleated lymphocytes (MN/1,000 BNC) in exposed workers and 6.0 (IQR 4.0-8.3) MN/1,000 BNC in non-exposed workers before shift. After shift, we observed 6.5 (IQR 4.4-9.3) MN/1,000 BNC in exposed workers and 6.5 (IQR 4.0-9.0) MN/1,000 BNC in non-exposed workers. Regression models were applied with the log-transformed MN frequency as the dependent variable in order to estimate the effects of exposure to vapours and aerosols of bitumen and of potential confounders. Age was the strongest predictor of MN formation in both exposed workers and referents. Our data suggest that MN formation was not associated with concentration of vapours and aerosols of bitumen during shift at the individual level. Although similar MN frequencies were observed in both groups, the modelling of factors potentially influencing MN frequency revealed a weak group difference in the post-shift model. We conclude that this small difference cannot be judged to be a relevant mutagenic effect of exposure to vapours and aerosols of bitumen, also with regard to the lack of adjustment for multiple testing and the lack of a group effect in the original data.     

Increased frequency of chromosomal aberrations and sister chromatid exchanges in peripheral lymphocytes of radiology technicians chronically exposed to low levels of ionizing radiations

Chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) frequencies were estimated in peripheral lymphocytes from 21 radiology technicians, and from 21 non-exposed control subjects. We exclusively considered individuals who neither smoke nor consume drugs or alcohol for a period of at least two years prior to the analysis. Significant differences were found between exposed and controls in terms of SCEs and CAs frequencies.Technicians showed a significant higher number of high-frequency individuals (HFIs) with respect to the control group. Nevertheless, the mean frequency of SCEs observed among technician HFIs did not significantly differ with respect to that observed among control HFIs. Vice versa, the non-HFIs belonging to technicians group showed a statistically higher difference in the SCEs/NSM value with respect to the non-HFIs belonging to control group. Since the differences in the SCEs frequencies between the two groups are due to non-HFIs, our results seem to indicate a general genotoxic effect of the IR, not affected by HFIs.Among technicians, the level of chromosome damage correlated neither with years of radiation exposure nor with the age of the subjects. Vice versa, in the control group, a positive correlation was found between the number of SCEs and age. In both samples the gender status did not influence the frequencies of CAs and SCEs.Our results suggest that chronic long-term exposure to low doses of ionizing radiation could increase the CAs and SCEs frequencies. This study reinforces the relevance of the biomonitoring of hospital workers chronically exposed to ionizing radiation.     

Analyses of micronuclei in exfoliated epithelial cells from individuals chronically exposed to arsenic via drinking water in inner Mongolia, China.

The groundwater in Bayingnormen (Ba Men), located in Central West Inner Mongolia, China, is naturally contaminated with arsenic at concentrations ranging from 50 microg/L to 1.8 mg/L. Various adverse health effects in this region, including cancer, have been linked to arsenic exposure via drinking water. A pilot study was undertaken to evaluate frequencies of micronuclei (MN), as measures of chromosomal alterations, in multiple exfoliated epithelial cell types from residents of Ba Men chronically exposed to arsenic via drinking water. Buccal mucosal cells, airway epithelial cells in sputum, and bladder urothelial cells were collected from 19 residents exposed to high levels of arsenic in drinking water (527.5 +/- 24 microg/l), and from 13 control residents exposed to relatively low levels of arsenic in drinking water (4.4 +/- microg/L). Analytical results from these individuals revealed that MN frequencies in the high-exposure group were significantly elevated to 3.4-fold over control levels for buccal and sputum cells, and to 2.7-fold over control for bladder cells (increases in MN frequency significant at p < .001 for buccal cells; p < .01 for sputum cells; p < .05 for bladder cells). When smokers were excluded from high-exposure and control groups the effects of arsenic were observed to be greater, although only in buccal and sputum cells; approximately 6-fold increases in MN frequency occurred in these tissues. The results indicate that residents of Ba Men chronically exposed to high levels of arsenic in drinking water reveal evidence of genotoxicity in multiple epithelial cell types; higher levels of induced MN were observed in buccal and sputum cells than in bladder cells.     

Assessment of micronuclei and sister chromatid exchange frequency in the petroleum industry workers in province of Vojvodina,Republic of Serbia

Persons who work with petroleum and petroleum derivatives (PPD) are potentially at risk of developing cancer mostly due to the carcinogenity of benzene. Therefore, the aim of this study was to determine in which degree occupational exposure of workers to PPD causes damage to DNA by analysis of micronuclei (MN), sister chromatid exchanges (SCE) and proliferation index (PI). 30 workers of refinery in Novi Sad, participated in the study as exposed and 30 volunteers as control group. Workers exposed to PPD had significantly higher values of MN and SCE in comparison to controls. Exposition time to PPD and type of working place have also significantly effects to DNA damage. The influence of confounding factor such as smoking and age were also evaluated.     

The effects of food protector biphenyl on sister chromatid exchange, chromosome aberrations, and micronucleus in human lymphocytes

The aim of this study was to determine the possible genotoxic effects of biphenyl (E230), which is used as an antimicrobial agent in food by using sister chromatid exchanges (SCEs), chromosome aberrations (CAs), and micronucleus (MN) tests in human peripheral lymphocytes. The human peripheral lymphocytes were treated with four concentrations of biphenyl (10, 30, 50, and 70 microg/mL) for 24- and 48-h treatment periods. In the present study, biphenyl significantly increased the frequency of SCEs, CAs, and the frequency of MN when compared with both untreated control and solvent (dimethyl sulfoxide) control. The inductions of these abnormalities were in a dose-dependent manner. Biphenyl was capable to induce the structural CAs instead of numerical CAs. Biphenyl also showed a cytotoxic effect by decreasing the replication index at the highest two concentrations for 48 h and nuclear division index at the highest two concentrations for the 24- and 48-h treatment periods. However, biphenyl did not affect the mitotic index (MI).     

Evaluation of primary DNA damage, cytogenetic biomarkers and genetic polymorphisms for CYP1A1 and GSTM1 in road tunnel construction workers

In tunnel construction workers, occupational exposure to dust (alpha-quartz and other particles from blasting), gases (nitrogen dioxide, NO(2)), diesel exhausts, and oil mist has been associated with lung function decline, induction of inflammatory reactions in the lungs with release of mediators that may influence blood coagulation, and increased risk of chronic obstructive pulmonary disease. The present molecular epidemiology study was designed to evaluate whether occupational exposure to indoor pollutants during road tunnel construction might result in genotoxic effects. A study group of 39 underground workers and a reference group of 34 unexposed subjects were examined. Primary and oxidative DNA damage, sister-chromatid exchanges (SCE), and micronuclei (MN) were measured in peripheral blood cells. The possible influences of polymorphisms in gene encoding for CYP1A1 and GSTM1 xenobiotic-metabolizing enzymes were also investigated. Exposure assessment was performed with detailed interviews and questionnaires. There were no significant differences in the level of primary and oxidative DNA damage and frequency of SCE between the tunnel workers and controls, whereas the frequency of MN showed a significant increase in exposed subjects compared to controls. No effects of CYP1A1 or GSTM1 variants were observed for the analyzed biomarkers. Since MN in peripheral blood lymphocytes are recognized as a predictive biomarker of cancer risk within a population of healthy subjects, the genotoxic risk of occupational exposure to various indoor environmental pollutants during road tunnel construction cannot be excluded by this biomonitoring study.     

The Effects of Food Protector Biphenyl on Sister Chromatid Exchange,Chromosome Aberrations,and Micronucleus in Human Lymphocytes

The aim of this study was to determine the possible genotoxic effects of biphenyl (E230), which is used as an antimicrobial agent in food by using sister chromatid exchanges (SCEs), chromosome aberrations (CAs), and micronucleus (MN) tests in human peripheral lymphocytes. The human peripheral lymphocytes were treated with four concentrations of biphenyl (10, 30, 50, and 70 μg/mL) for 24- and 48-h treatment periods. In the present study, biphenyl significantly increased the frequency of SCEs, CAs, and the frequency of MN when compared with both untreated control and solvent (dimethyl sulfoxide) control. The inductions of these abnormalities were in a dose-dependent manner. Biphenyl was capable to induce the structural CAs instead of numerical CAs. Biphenyl also showed a cytotoxic effect by decreasing the replication index at the highest two concentrations for 48 h and nuclear division index at the highest two concentrations for the 24- and 48-h treatment periods. However, biphenyl did not affect the mitotic index (MI).     

Frequency of sister chromatid exchange in chrysotile-exposed workers.

Chrysotile, which is an industrial carcinogen, has been shown to induce a dose-dependent increase in the frequency of sister chromatid exchange (SCE) in vitro. Authors designed this study to examine the increase of SCEs frequency in the workers occupationally exposed to chrysotile. Heparinized whole blood samples from 45 chrysotile-exposed and 45 control volunteers were cultured for 72 h. The significant difference of SCE frequency was found between chrysotile-exposed workers and control group. The highest SCEs frequency was found in chrysotile-exposed smokers, and the lowest in control non-smokers. The effect of chrysotile exposure on SCEs was marginally significant after controlling the effects of age and smoking by multiple regression analysis.     

Cytogenetic biomarkers, urinary metabolites and metabolic gene polymorphisms in workers exposed to styrene

The present study comprised a biomonitoring study in 95 workers occupationally exposed to styrene and 98 unexposed controls, employing an integrated approach involving biomarkers of exposure, effect, and susceptibility. Airborne styrene was evaluated at workplace, and urinary styrene metabolites, mandelic acid (MA), phenylglyoxylic acid (PGA), vinylphenols (VPTs) and phenylhydroxyethylmercapturic acids (PHEMAs), were measured as biomarkers of internal dose. Cytogenetic alterations were evaluated by analysing the frequency of chromosomal aberrations (CAs) and micronucleated binucleated cells (MNBN) in peripheral blood lymphocytes. The micronucleus assay was coupled with centromeric fluorescence in situ hybridization to distinguish micronuclei (MN) arising from chromosomal breakage (C- MN) from those harboring whole chromosomes (C+ MN). The possible influence of genetic polymorphisms of xenobiotic-metabolizing enzymes involved in styrene biotransformation (EPHX1, GSTT1, GSTM1, GSTP1) and NAT2 on the cytogenetic endpoints was investigated. The exposed workers showed a significantly higher frequency of MNBN (13.8+/-0.5% versus 9.2+/-0.4%; P<0.001) compared to control subjects. The effect appeared to concern both C- and C+ MN. A positive correlation was seen between the frequency of C+ MN and urinary level of MA+PGA (P<0.05) and VPTs (P<0.001). Chromosome-type CAs positively correlated with airborne styrene level and VPTs (P<0.05), whereas chromatid-type CAs correlated with PHEMAs (P<0.05). Workers bearing GSTM1 null genotype showed lowered levels of PHEMAs (P<0.001). The GSTT1 null genotype was associated with increased MNBN frequencies in the exposed workers (P<0.05) and the fast activity EPHX genotype with a moderate decrease in both MNBN and CAs in the controls. Our results suggest that occupational exposure to styrene has genotoxic effects that are potentiated by the GSTT1 gene deletion. These observations may have relevance considering the risk of lymphatic and haematopoietic malignancies tentatively associated with styrene exposure.     

Effects of natamycin on sister chromatid exchanges,chromosome aberrations and micronucleus in human lymphocytes

Natamycin (pimaricin) (E235) is an antifungal that can be used as an antibiotic to treat most fungus infections. It has been globally used in a variety of foods and beverages. In the present study, the effects of natamycin on chromosome aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) formation in human lymphocytes cells were investigated. The human lymphocytes were treated with 13, 18, 23, and 28 μg/mL of natamycin for 24 and 48 h. Natamycin induced the SCE frequency at the highest concentration for 48 h only; however, it induced the structural CA and MN frequency at all concentrations when compared to control and at all concentrations, except the lowest concentration (13 μg/mL), when compared to solvent control. Natamycin showed a cytotoxic effect by decreasing the replication index, mitotic index, and nuclear division index (NDI), especially at the highest concentrations for two treatment periods.     

Genotoxic damage in hospital workers exposed to ionizing radiation and metabolic gene polymorphisms

Of all workers exposed globally to synthetic sources of radiation, medical personnel represent the largest group, but receive relatively low doses. Accidental or therapeutic acute radiation exposure of humans was observed to induce various forms of cytogenetic damage, including the possibility of increasing the incidence of micronuclei (MN) and chromosomal aberrations (CA). The aim of this study was to assess occupationally induced chromosomal damage in a large population of hospital workers exposed to low doses of ionizing radiation (IR). The cytokinesis-block MN and comet assays were used to examine peripheral blood lymphocytes (PBL) of 31 exposed workers to IR and 33 control subjects corresponding in gender, age, and smoking. Glutathione S-transferases (GSTM1, GSTT1, and GSTP1) are postulated to be involved in the detoxification of endogenous and exogenous genotoxicants. The association between these biomarkers and polymorphic genes of xenobiotic metabolizing enzymes was thus also assessed. MN frequency was significantly higher in the exposed subjects compared controls. Comet assay results showed a significant increase of tail length in workers exposed to IR. Data obtained suggest that GSTM1, GSTT1, and GSTP1 polymorphism do not modify significantly the genotoxic potential of IR. Therefore, the exposed medical personnel need to carefully apply radiation protection procedures and minimize, as low as possible, IR exposure to avoid possible genotoxic effects.     

Carcinoembryonic antigen, alpha-fetoprotein, and prostate-specific antigen in the sera of industrial workers exposed to phenol, formaldehyde, urea, and mixed vapors

Exposure to certain industrial agents has been thought to have carcinogenic potential, both for employees who work closely with agents and for the general population that comes into contact with them. The objective of the present study is to evaluate the changes at the cellular level or at the level of cellular metabolism products present in the biological fluid, and to detect early stages of the carcinogenic process resulting from the exposure of industrial environmental hazards. Carcinoembryonic antigen (CEA), alpha-fetoproteins (AFP), and prostate-specific antigen (PSA) were measured in sera of workers (n = 51), who were divided into 4 groups: group I, workers exposed to phenol; group II, workers exposed to formaldehyde; group III, workers exposed to urea; and group IV, workers exposed to mixed vapor, plus a reference control healthy group (n = 15). The results showed that 75% of the workers exposed to phenol, 75% of the workers exposed to urea, 83.3% of workers exposed to formalin, and 92.3% of the workers exposed to mixed vapors had raised values of serum CEA (S-CEA) above normal value of the control group. Also, 23% of workers exposed to mixed vapors, 44% of workers exposed to formalin, 50% of workers exposed to phenol, and 62.5% of workers exposed to urea had raised values of serum AFP (S-AFP) above normal value of control group. Finally, 16.6% of workers exposed to phenol, 23% of workers exposed to mixed vapors, and 33.3% of workers exposed to formalin had raised values of serum PSA (S-PSA) above the normal value of control group; there were no raised values of S-PSA in workers exposed to urea. No significant difference was found in the activities of AST and ALT in group I, but a highly significant increase was found in the AST activities for groups II and IV and the ALT activities for groups III and IV. A significant difference was found in the activity of ALT in group II and in AST for group III. There was no significant difference in the levels of albumin in groups I, II, and III, whereas albumin levels were significantly decreased in group IV. No significant change was found in the level of urea and creatinine in all groups except for group III, where serum levels of creatinine were significantly decreased. From our findings, we concluded that S-CEA can be used as an important prognostic screening marker for early prediction for malignancy, and for management of workers with lung cancer who are exposed to the environmental hazards in industrial factories. Furthermore, S-AFP can be used also as a biomarker if it is carried out and correlated with S-CEA.     

Comparison of internal dose measures of solvents in breath, blood and urine and genotoxic changes in aircraft maintenance personnel

Solvents and fuels are in widespread use both in civilian and military populations. 1,1,1-trichloroethane (TCA), xylene, toluene, methyl ethyl ketone (MEK) and methylene chloride are found in a variety of compounds including degreasing agents, paints, coatings, pesticides and paint strippers. Toluene and xylene are also found in fuels, which are complex mixtures of hundreds of agents. The purpose of this investigation was twofold. The first was to determine the optimum medium to measure internal dose of solvents comparing blood, urine and breath. The second was to determine if low level exposures were associated with genotoxic changes after a short-term exposure of fifteen or thirty weeks. To accomplish the first goal a pilot study was initiated involving eight volunteers who worked in aircraft maintenance including sheet metal, painting and assembly mechanic jobs. Industrial hygiene measurements were evaluated over 30 working days. Breath, blood and a 24-hour urine sample were collected twice to compare internal dose parameters. To achieve the second goal, 58 newly hired subjects were monitored prior to exposure and over 30 weeks to determine if there were genotoxic changes as a result of solvent and/or fuel exposure as measured by sister chromatid exchanges (SCEs) and micronuclei (MN). Exposure groups included workers involved in sheet metal (fuel cell) activities, painting, fueling operations and flight line. Results of the pilot study demonstrated that industrial hygiene air samples and internal breath measures taken on the same day were highly correlated for measuring TCA (r = 0.93) and toluene (r = 0.90) but was not as well correlated for the other compounds. Breath measures were more sensitive for measuring low level exposure than were either analytes in blood or 24-hour urine samples; these latter two measures were usually below the limit of detection. A small but statistically significant increase in the frequency of SCEs occurred after 30 weeks of exposure for sheet metal workers (p = 0.003) and for painters (p = 0.05). The MN frequency in the sheet metal workers initially showed a significant increase by 15 weeks, but by 30 weeks had decreased. Chance occurrence of exposures to other occupational or non-occupational agents can not be eliminated as a cause of the genotoxic results since between 58 and 93 total analytes could be found in the breath of some aircraft maintenance personnel.     

Carcinoembryonic Antigen,Alpha-fetoprotein,and Prostate-Specific Antigen in the Sera of Industrial Workers Exposed to Phenol,Formaldehyde, Urea,and Mixed Vapors

Exposure to certain industrial agents has been thought to have carcinogenic potential, both for employees who work closely with agents and for the general population that comes into contact with them. The objective of the present study is to evaluate the changes at the cellular level or at the level of cellular metabolism products present in the biological fluid, and to detect early stages of the carcinogenic process resulting from the exposure of industrial environmental hazards. Carcinoembryonic antigen (CEA), alpha-fetoproteins (AFP), and prostate-specific antigen (PSA) were measured in sera of workers (n = 51), who were divided into 4 groups: group I, workers exposed to phenol; group II, workers exposed to formaldehyde; group III, workers exposed to urea; and group IV, workers exposed to mixed vapor, plus a reference control healthy group (n = 15). The results showed that 75% of the workers exposed to phenol, 75% of the workers exposed to urea, 83.3% of workers exposed to formalin, and 92.3% of the workers exposed to mixed vapors had raised values of serum CEA (S-CEA) above normal value of the control group. Also, 23% of workers exposed to mixed vapors, 44% of workers exposed to formalin, 50% of workers exposed to phenol, and 62.5% of workers exposed to urea had raised values of serum AFP (S-AFP) above normal value of control group. Finally, 16.6% of workers exposed to phenol, 23% of workers exposed to mixed vapors, and 33.3% of workers exposed to formalin had raised values of serum PSA (S-PSA) above the normal value of control group; there were no raised values of S-PSA in workers exposed to urea. No significant difference was found in the activities of AST and ALT in group I, but a highly significant increase was found in the AST activities for groups II and IV and the ALT activities for groups III and IV. A significant difference was found in the activity of ALT in group II and in AST for group III. There was no significant difference in the levels of albumin in groups I, II, and III, whereas albumin levels were significantly decreased in group IV. No significant change was found in the level of urea and creatinine in all groups except for group III, where serum levels of creatinine were significantly decreased. From our findings, we concluded that S-CEA can be used as an important prognostic screening marker for early prediction for malignancy, and for management of workers with lung cancer who are exposed to the environmental hazards in industrial factories. Furthermore, S-AFP can be used also as a biomarker if it is carried out and correlated with S-CEA.     

Influence of GSTs, CYP2E1 and mEH polymorphisms on 1, 3-butadiene-induced micronucleus frequency in Chinese workers

1,3-butadiene (BD) has been classified as a human carcinogen, however, the relationship between chromosomal damage and its metabolic polymorphisms is not clear. The present study used the CBMN assay to detect chromosomal damage in the peripheral lymphocytes of 166 exposed workers and 41 non-exposed healthy individuals. PCR and PCR-RFLP were applied to detect GSTT1, GSTM1, CYP2E1 c1c2 and mEH Tyr113His, His139Arg polymorphisms. The results demonstrated that the micronucleus (MN) frequency of the exposed workers was significantly higher than controls (P < 0.01). Among the exposed workers, the individuals with high BD exposures are more susceptible to chromosomal damage than those with low exposures (FR = 1.30, 95% CI 1.14-1.53; P < 0.05). Gender-difference was also found in our study: males got lower micronucleus frequency than females. Workers who carried the genotypes of GSTM1 (+), CYP2E1 (c1c2/c2c2) and mEH intermediate (I) group had significantly higher MN frequency than those carrying the genotypes of GSTM1 (−) (FR = 1.29, 95% CI 1.05-1.59; P < 0.05), CYP2E1 (c1c1) (FR = 1.55, 95% CI 1.24-1.93; P < 0.01) or mEH high (H) group (FR = 1.57, 95% CI 1.08-2.34; P < 0.05), respectively. Our data indicated that the current BD exposure level could cause significantly higher MN frequency in workers than controls. Polymorphisms of GSTM1, CYP2E1 and mEH are susceptible to altered chromosome damage.     

Association of the NQO1, MPO, and XRCC1 polymorphisms and chromosome damage among workers at a petroleum refinery

Benzene is a leukemogen, and exposure to benzene is an occupational hazard in the petroleum refining industries. The effects of genetic polymorphisms in the NQO1 (rs1800566), MPO (rs2333227), and XRCC1 (rs25487) genes on benzene-induced chromosome abnormalities were assessed in 108 benzene-exposed workers and 33 office workers. The mean benzene exposure for exposed workers was 0.51 ppm for full-shift workers, and the time-weighted average ranged from 0.004 to 4.25 ppm. The frequencies of micronuclei (MN) and chromosome aberrations (CA) were significantly higher in workers exposed to benzene than unexposed controls. Exposed workers with the T/T genotype for NQO1 showed significant 1.9-fold (95% CI = 1.5-2.3) and 2.6-fold (95% CI = 1.7-3.9) increases in MN and CA frequencies, respectively, compared to controls with C/C and C/T genotypes, after adjusting for age, smoking status, and alcohol intake. Among exposed workers, subjects with the combination of MPO G/G and XRCC1 Arg/Gln or Gln/Gln showed a significantly higher CA frequency compared to those with the combination of MPO G/A or A/A and XRCC1 Arg/Arg genotypes. These results indicated that the genotoxicity induced by a chronic benzene exposure is modulated by genes involved in both DNA repair and benzene metabolic pathways.