Sister chromatid exchanges in rotogravure printing plant workers

Objective: The individual burden of inhaled ambient-air toluene and its link to genotoxic phenomena in exposed printing workers. Method: The influence of toluene on sister chromatid exchange (SCE) was investigated by monitoring of the individual toluene burden of 42 exposed printing workers. Therefore, the urinary hippuric acid (HA) excretion was measured directly after the work shift. The results were compared with those recorded for a control group consisting of 45 blood donors. SCE frequencies were determined from peripheral lymphocytes for both groups. Results: The median HA excretion of the exposed and nonexposed groups amounted to 1.94 and 0.45?g/g creatinine, respectively. For both groups, different SCE rates were detected: 10.13 and 6.84 counts/lymphocyte for exposed and nonexposed persons, respectively. The independence of the measured values proved to be significant at a high confidence level (P=0.000) for both groups. The influences of smoking and alcohol consumption on SCE as well as on HA values could be clearly separated from those induced by toluene. Conclusions: The results of our study indicate a strong relationship between the individual toluene burden and the genotoxic risk of the exposed persons. Since toluene was used for dilution of the letter-press ink, the influence of ink mist on the genotoxic effects could not be completely excluded.     

DNA-protein cross-links and sister chromatid exchange frequencies in lymphocytes and hydroxyethyl mercapturic acid in urine of ethylene oxide-exposed hospital workers

The lymphocytes of 25 hospital workers exposed to ethylene oxide and of a standardized control group were investigated for DNA damage (measured by alkaline filter elution) and sister chromatid exchange (SCE) frequencies. Additionally, the excretion of hydroxyethyl mercapturic acid (HEMA) in the 24-h urine of ten workers and ten control persons was determined. The peak levels of ethylene oxide in air during the first 8 min after opening of the sterilization unit were measured. Peak levels of ethylene oxide in the air of up to 417 ppm after opening of the sterilization unit were detected. In the alkaline filter elution assay we found significantly reduced elution rates in the exposed workers, indicating DNA-protein cross-links. The reduction of the elution rates through HVLP filters correlated significantly with the exposure classification (low, medium, high) (r = –0.45, P < 0.05) and the ethylene oxide peak level after opening of the sterilization unit (r = –0.42, P < 0.05). The SCE frequencies in the standardized control group were significantly elevated. With respect to (n = 78) historic control SCE values of our institute, the SCE values of the disinfectors were not significantly elevated (6.54 vs 6.27). The ethylene oxide-exposed workers did not have a greater percentage of high-frequency SCE cells. The mean HEMA concentration in the urine of the exposed workers was significantly elevated, but there were wide variations in HEMA concentrations and no correlation to ethylene oxide exposure. We conclude that the alkaline filter elution assay may be a sensitive parameter for monitoring the genotoxic damage in lymphocytes of ethylene oxide-exposed workers. Determination of the HEMA concentration in urine may be suitable for the differentiation between ethylene oxide-exposed and nonexposed groups, but not for individual biomonitoring. The result of the SCE determination indicates that the standardization of control groups with respect to sex, age, and smoking habit seems unsatisfactory. Therefore, it is recommended that in further studies control groups be constructed with respect to additional lifestyle factors. Additionally, enzyme polymorphisms — especially of glutathione transferase in the case of ethylene oxide exposure — should be taken into consideration and controlled.     

Frequency of sister chromatid exchange and chromosomal aberrations in asbestos cement workers.

Exposure to asbestos minerals has been associated with a wide variety of adverse health effects including lung cancer, pleural mesothelioma, and cancer of other organs. It was shown previously that asbestos samples collected from a local asbestos factory enhanced sister chromatid exchanges (SCEs) and chromosomal aberrations in vitro using human lymphocytes. In the present study, 22 workers from the same factory and 12 controls were further investigated. Controls were matched for age, sex, and socioeconomic state. The peripheral blood lymphocytes were cultured and harvested at 48 hours for studies of chromosomal aberrations and at 72 hours for SCE frequency determinations. Asbestos workers had a raised mean SCE rate and increased numbers of chromosomal aberrations compared with a control population. Most of the chromosomal aberrations were chromatid gap and break types.     

Evaluation of sister chromatid exchange and chromosomal aberration frequencies in peripheral blood lymphocytes of gasoline station attendants

Petroleum derivatives constitute a complex mixture of chemicals which contain well-known genotoxicants, such as benzene. Thus, chronic occupational exposure to such derivatives may be considered to possess genotoxic risk. In the present study, frequencies of sister chromatid exchange (SCE); aberrant cells, including numerical and structural chromosomal aberrations; and chromosome aberrations were investigated in peripheral blood lymphocytes from 30 exposed workers (15 smokers and 15 nonsmokers) and 30 controls (15 smokers and 15 nonsmokers). The exposed subjects were employed at 12 different petrol pumping stations in the city of Mersin, Turkey. Urinary phenol levels of exposed workers were found to be significantly higher than those of control subjects. Benzene exposure and cigarette smoking decrease the replication index and mitotic index. There is an interaction between benzene exposure and cigarette smoking for replication index and mitotic index. There is no interaction between cigarette smoking and benzene exposure for chromosomal aberrations. The results indicate that there are significant differences in SCE values in the exposed workers compared to the control individuals (P < 0.01), but there is no difference between smokers and nonsmokers for SCE frequency (P > 0.05). SCE frequency is higher in smokers than in nonsmokers.     

Sister chromatid exchanges and DNA repair capability in sanitary workers exposed to ethylene oxide: evaluation of the dose-effect relationship

Determination of ethylene oxide (EtO) in the working environment and induction of sister chromatid exchanges (SCE) and unscheduled DNA synthesis (UDS) in peripheral lymphocytes of 10 exposed sanitary workers and 10 control subjects matched for sex, age, and smoking habits are reported. The relationship between the external dose of EtO and the frequency of SCE was determined in the above group and in a group of 41 sanitary workers previously studied. The 10 newly examined workers were exposed to EtO concentrations (1.84 ppm as time-weighted average) intermediate between the high (10.7 ppm) and low (0.35 ppm) levels of exposure of the two previously examined groups (19 and 22 workers, respectively). A statistically significant (p less than 0.002) increase of SCE frequency was observed between the present control and exposed groups. The inducibility of unscheduled DNA synthesis by gamma rays was lower in the lymphocytes of the exposed workers than in controls, but the difference was not statistically significant. A significant relationship between the frequency of SCE and the level of EtO exposure for the three exposed groups was demonstrated by two different statistical methods. It is suggested that the present Italian threshold limit value for EtO (3 ppm) may not protect the exposed workers against possible genotoxic effects and that even a chronic exposure to 1 ppm may not be devoid of genotoxic risk.     

甲醛对从业工人外周血淋巴细胞的遗传学效应

甲醛(FA)是一种诱变剂,同时也是一种人类的可疑致癌剂。在多种体外诱变试验中都得到了阳性结果,在啮齿动物中,FA可以引起鼻腔部和鼻咽部癌。对上海石化总厂生产过程中接触FA的21名男性工人进行了染色体分析,14名非生产工人作为对照。FA生产环境中的空气浓度年平均为2.51mg/m3。结果与对照组比较,SCE没有显著改变,而染色体的畸变率明显高于对照组(P<0.05)。畸变类型包括单体型和染色体型两种,主要是单体断裂、无着丝点断片、双着丝点和非整倍体。证明FA是一种染色体断裂剂。我国1979年颁发的FA空气中最高容许浓度3mg/m3对长期职业接触FA的人群而言,仍是不安全的。     

Sister chromatid exchanges and chromosome aberrations in lymphocytes of medical personnel handling cytostatic drugs

Many anticancer drugs, including cytostatic drugs, are genotoxic. Evidence on human carcinogenicity has been conclusive. Persons handling these drugs might be exposed to an occupational health hazard, as they cause chromosomal damage in the lymphocytes. This study was conducted on 30 Egyptian medical personnel handling cytostatic drugs, working in the Medical Research Institute, Alexandria University and Gamal Abd El Naser Hospital in Alexandria. A control group comprised 30 normal healthy individuals matched for age and sex and had no contact with cytostatic drugs. Also, they were not exposed to any mutagenic agents. The workers and controls were interviewed to exclude exposure to any mutagenic agents other than anticancer drugs in case of medical workers. Cytogenetic methods were done to all subjects to assess chromosomal aberrations (CA) and sister chromatid exchanges (SCE). Significantly increased frequencies of CA and SCEs were found in exposed personnel as compared to the controls. Chromosomal aberrations and SCEs frequencies were not correlated with the age of exposed personnel and duration of exposures to cytostatic drugs. There was no increased risk of malformed children in exposed females and no history of repeated abortion. The results of this study point to the handling of cytostatic drugs as a possible genotoxic hazard. Therefore, effective protection and care in handling must be further emphasized to prevent adverse effects.     

低浓度环氧丙烷的细胞遗传学效应研究

为探讨低浓度环氧丙烷的细胞跗学效应,对４６名环氧丙烷作业工人和７４名对照工人外周血淋巴细胞染色体畸变、微核、姐妹染色单体交换进行了检测分析。结果表明,环氧丙烷接触组工人外周因细胞姐妹染色单体交换率显著高于对照组,而染色体畸变率和微核率两组间均无显著性差异,提示低浓度环氧丙烷具有细胞遗传学毒性,可导致ＤＮＡ损伤。     

补硒对砷接触工人细胞遗传物质损伤作用的观察

An increased chromosomal aberration and micronuclei rate of cultured lymphocytes among smelter workers in Yunnan Tin Corporation has been associated with exposure to arsenic which might be involved in carcinogenesis of lung cancer in this area. Selenium, as an essential trace element for life, antagonizes the toxic effects of arsenic. The low intake of selenium among workers in this area might increase injurious effects of arsenic in the tissues. The preliminary results showed that the chromosomal aberration rate of cultured lymphocytes in smelter workers was lowered about 46.1% after treatment with selenium 150 micrograms/d for 21 days. It will provide clues for further study on the elimination of toxicity of arsenic among workers who are exposed to arsenic by supplementation of selenium.     

Sister chromatid exchange (SCE)and high-frequency cells in workers professionally exposed to extremely low-frequency magnetic fields (ELF)

BACKGROUND: Up now no firm conclusions can be drawn on the genotoxicity of Extremely Low Frequency (ELF) Magnetic Fields (MF) in exposed workers: both an increase in chromosomal aberrations (CA) and micronuclei (MN) or no effects were observed in substation workers, while a slight increase in CA, but not in sister chromatid exchanges (SCE) or MN was reported in linesman; an increase in CA was observed in cable splicers and, more recently, in train engine drivers, but results have not been replicated. OBJECTIVES: Objective of the study was an evaluation of possible genotoxicity of occupational exposure to ELF-MF. METHODS: SCE, high-frequency cells (HFC) and SCE in HFC were measured in peripheral blood lymphocytes from 70 workers exposed to various levels of ELF-MF in different occupations, not involving exposure to known mutagens or carcinogens. In all participants, individual ELF-MF exposure was measured throughout the whole work-shift for 3 consecutive days by personal monitoring. RESULTS: Time Weighted Average (TWA) values of ELF-MF in the whole group ranged from 0.01 to 3.48 microT; the geometric mean was 0.19 mT, and only 3 subjects exceeded 2 microT. According to the individual TWA exposure, subjects were divided into two groups: low exposed (< or = 0.2 microT) and highly exposed (> 0.2 microT). The mean values of SCE, HFC and SCE in HFC were compared between low and highly exposed: no significant differences were observed. The result was further tested by selection and comparison of workers exposed up to 0.1 microT vs. exposed > 0.4 microT only, i.e. excluding intermediate exposures: again no difference in genotoxicity indices was observed. Also multivariate analysis did not show any correlation between individual ELF-MF exposure and genotoxicity indices. CONCLUSIONS: The results of our study do not give any support to the hypothesis that occupational exposure to ELF-MF up to about 2 microT, i.e. at the levels currently found in most workplaces, can exert a genotoxic effect in workers.     

Cytogenetic changes in persons exposed to polychlorinated biphenyls]

A cytogenetic study performed in a group of workers exposed to polychlorinated biphenyls comprised analysis of structural chromosomal aberrations in the lymphocytes in the first division in vitro, analysis of micronuclei frequency in binuclear lymphoblasts induced by cytochalasin B and analysis of sister chromatid exchanges. The study included 48 exposed workers and 15 controls. In 16 exposed workers increased incidence of unstable chromosomal aberrations (dicentrics, rings and acentrics) was found, while in 19 no structural chromosomal aberrations could be detected. In 11 workers changes defined as chromosomal and chromatid breaks were noted. This type of change, however, can be evidenced in a non-exposed population as well. In two workers stable chromosomal aberrations were recorded (translocations and inversions). The incidence of micronuclei as well as exchange of sister chromatids were elevated in the exposed group of workers compared to controls.     

Biological monitoring of hospital pharmacy personnel occupationally exposed to cytostatic drugs: urinary excretion and cytogenetics studies

For evaluation of the risk borne by hospital pharmacy personnel exposed to antineoplastic agents, the incorporation of cyclophosphamide, ifosfamide, and platinum-containing drugs was quantified by the determination of urinary concentrations. In addition, the induction of micronuclei (MN) and sister-chromatid-exchange (SCE) rates in peripheral blood lymphocytes were studied for correlation with the urinary excretion of cytostatic drugs. Cyclophosphamide and ifosfamide were determined in 24-h urine samples using gas chromatography with electron capture (detection limit 2.5 μg/l). Voltammetric analysis enabled the determination of platinum concentrations of 4 ng/l. Heparinized blood (20 ml) was drawn and lymphocytes were cultured for MN and SCE studies. In all, 13 hospital pharmacists and pharmacy technicians regularly involved in the preparation of cytostatic drugs participated in this investigation (7 persons represent a follow-up group). All subjects applied standard safety precautions, including the use of a vertical laminar air-flow hood, protective gowns, and latex gloves. On the day of urine sampling an average of 4,870 mg cyclophosphamide, 5,580 mg ifosfamide, and 504 mg platinum-containing drugs were handled. The excretion of 5 and 9 μg cyclophosphamide/1 urine was measured in two samples, respectively. An elevated level of urinary platinum was found in one pharmacist (22.3 ng/g creatinine) in comparison with a nonexposed control group. Mean frequencies of MN and SCE did not differ significantly between the drug exposed group and control group. The employees who had incorporated chemotherapeutic agents were part of the follow-up group and, thus, particularly cautious and sensitive to a possible hazard. The results emphasize the necessity of improving personal protection of hospital pharmacy personnel occupationally exposed to cytostatic drugs and support the importance of biological monitoring. In an ongoing project in our department the sources of contamination are being investigated parallel to biological monitoring so as to determine critical situations and improve personal protection. Received: 7 August 1996 / Accepted: 3 January 1997     

Ethylene oxide: an overview of toxicologic and epidemiologic research

Ethylene oxide (EtO) is a reactive epoxide and potent biocide. It is used widely in gas sterilization of hospital equipment. An estimated 75,000 health care workers in the United States have potential exposure. EtO binds covalently to deoxyribonucleic acid (DNA) and has been shown in 13 species to cause point mutations. Apparently, as a consequence of its alkylating ability, EtO exposure can result in chromosomal damage. In monkeys EtO exposure produces increased frequencies of sister chromatid exchanges (SCEs) and chromosomal aberrations. In man, five cytogenetic studies have shown dose-related increased frequencies of either SCE or chromosomal aberrations; in one study SCEs developed after regular exposures lasting less than five minutes per day. EtO is a reproductive toxin. In adult male rats, exposure produces decreased fertility, increased fetal deaths, and heritable chromosomal translocations. In pregnant female rats and rabbits, exposure causes increased fetal losses, and in one study in pregnant mice exposure was associated with increased numbers of malformed fetuses. In male monkeys EtO causes dose-related reductions in sperm count and sperm motility. In pregnant women, one study suggests that brief occupational exposure twice daily in concentrations of 20 ppm or above was associated with increased spontaneous abortions. EtO is carcinogenic to animals. In rats it causes dose-related increases in mononuclear cell leukemias, peritoneal mesotheliomas, and cerebral gliomas. In man, exposure has been associated in two epidemiologic studies with increased leukemias: 3 leukemias observed versus 0.2 expected in one study, and 2 observed versus 0.14 expected in the other; two additional small studies of limited power found no excess leukemias. Quantitative risk assessment indicates that from 634 to 1,093 excess deaths from cancer will occur per 10,000 workers exposed to EtO at 50 ppm over a working lifetime, and that 12 to 23 excess cancer deaths will occur per 10,000 workers exposed at 1 ppm. The National Institute for Occupational Safety and Health (NIOSH) recommends that EtO be regarded as a potential human carcinogen. NIOSH has recommended that eight-hour time-weighted average exposure to EtO be less than 0.1 ppm and that short-term peak exposure not exceed 5 ppm for more than ten minutes per working day.     

Association between urinary 1-hydroxypyrene and genotoxic effects in coke oven workers

Methods: Blood and urine samples were collected immediately after a shift at the end of a working week from 50 coke oven workers and 50 control workers not exposed to PAHs. Methods included: (1) biomarkers of exposure: urinary 1-hydroxypyrene (HpU), urinary mutagenicity by the plate Salmonella test with strains TA98 and YG1024 after metabolic activation, expressed as mutagenic rate (MR98 and MR1024, respectively), urinary cotinine; and (2) biomarkers of biological effects in peripheral blood lymphocytes (PBL): sister chromatid exchanges (SCE/cell), cells of high frequency of SCE (% HFC), micronuclei (MN/1000 cells), chromosomal aberrations (CA/100 cells), and DNA damage by the Comet assay.

Results: Occupational exposure to PAH resulted in significantly increased levels of HpU and mutagenic effect of urine. Median values of these biomarkers in coke oven workers were: 9.0 µmol/mol creatinine for HpU, 2.7 for MR98, and 8.2 for MR1024, compared to the controls: HpU = 0.6 µmol/mol creatinine, MR98 = 1.2, and MR1024 = 5.5. Occupational exposure caused significant induction of SCE, HFC, and MN in coke oven workers: median SCE = 5.9, HFC = 12.0%, MN = 6.0 compared to the controls: 3.9, 5.0%, and 3.0, respectively. No effect of occupational exposure was found in relation to CA and DNA damage measured with the Comet assay. HpU concentration was positively associated with SCE and HFC. The concentration of urinary 1-hydroxypyrene corresponding to a 5% probability of increased SCE was 1.0 µmol/mol creatinine.

Conclusions: The occupational exposure to PAHs resulted in measurable biological effects (SCE, HFC, MN). In coke oven workers an increased level of SCE was not observed below the level of 1.0 µmol HpU/mol creatinine.

     

UDS and SCE in lymphocytes of persons occupationally exposed to low levels of ionizing radiation

Unscheduled DNA synthesis induced by in vitro UV irradiation was investigated in lymphocytes of persons occupationally exposed to low doses of ionizing radiation (maximum registered radiation dose: 98 mrad/month). For radiation exposures greater than 14 mrad/month above background level, increased rates of UDS after in vitro UV irradiation of lymphocytes were found. The bromodeoxyuridine differential chromatid labeling technique was applied to the examination of spontaneous and Mitomycin C (MMC)-induced sister chromatid exchanges (SCE) in the same population. No statistically significant difference could be determined in spontaneously occurring SCEs, while MMC induced SCEs were significantly reduced in persons exposed to radiation doses greater than 14 mrad/month, thus indicating increased repair capability for DNA lesions inflicted by a second insult after protracted low-dose irradiation.     

职业接触二甲苯女工的抗6-TG外周血淋巴细胞突变率的检测

本文对３０名职业接触二甲苯女工（年龄３５岁以下，工龄９年以上）的外周血淋巴细胞进行了６－ＴＧｒ的检测，同时选择相同年龄段的非接触二甲苯的女工作对照。检测结果表明，接触组与对照组之间没有显著差异（ｐ＞０．０５），说明二甲苯不能诱发体细胞突变。     

Sister chromatid exchange frequency in workers exposed to high levels of ethylene oxide,in a hospital sterilization service

Summary Blood samples were taken from a group of 25 subjects professionally exposed to high levels of ethylene oxide (EO) during the past two years; the samples were compared to those from 22 control subjects, using sister chromatid exchange (SCE) methodology. The quantity of ethylene oxide inhaled during the two previous years was subsequently evaluated to fall between 500 and 5800 mg. When compared with the control group, the exposed group demonstrated a significant increase in the SCE rate. For certain individuals, the rate of increase rose 100% beyond the control mean. Smoking habits significantly influenced the data observed for the control group, but no significant differences in the SCE rate were found for the exposed group, regardless of smoking habits. Senior workers had the highest SCE mean levels. This observation indicated that the effect of exposure to EO was sufficient to produce a genetic reaction, was cumulative and in some cases persistent.     

Studies of biological and chemical monitoring of low-level exposure to ethylene oxide

Ten sanitary workers exposed to concentrations of ethylene oxide below 1 ppm were studied to determine whether effects could be observed at low exposure levels. A significant increase in the number of sister chromatid exchanges in cultured lymphocytes was found only for five subjects with relatively high exposure in the sterilization area. However, it was not possible to separate clearly the effect of smoking from that of ethylene oxide exposure. No increase in the frequencies of micronuclei in lymphocytes and buccal cells was found. The level of 2-hydroxyethyl adducts to the N-terminal valines in hemoglobin responded in a reliable fashion to chronic ethylene oxide exposure and smoking. Furthermore, measurement of levels of 2-hydroxyethyl adducts to the N-terminal valines in hemoglobin made it possible to reconstruct the dynamics of a leakage of ethylene oxide which involved three workers.     

Thioether excretion of workers exposed to bitumen fumes

Summary The excretion of thioethers was determined in the urine of workers involved in road paving operations and in the preparation of asphalt mixing in an asphalt plant. An occupationally nonexposed group served as control. From the results it was observed that there was no significant difference in urinary thioether levels between the exposed and nonexposed groups, however, smokers of both exposed groups had significantly higher urinary thioether levels than the nonexposed smoking workers. These results suggested that higher urinary thioether excretion could be only due to a difference in smoking behaviour. There were also significant differences in urinary thioether levels between the exposed smoking and nonsmoking workers. The authors suggest that these workers have a low mutagenic/carcinogenic risk and smoking is responsible for the majority of thioether excretion, as has been found by other investigators.     

职业接触环氧丙烷工人Hb加合物及其遗传毒性分析

目的 研究长期接触低浓度环氧丙烷工人的遗传效应。方法 采用气相色谱法对环氧丙烷作业现场进行监测的同时,采集工人血样,采用高灵敏的N-alkyl Edman气质谱法对血红蛋白加合物(HP-缬氨酸)含量进行了测定,同时对姐妹染色单体互换(SCE)进行检测。结果 环氧丙烷作业工人时间加权平均浓度(TWA)为2．6mg/m^3和6．9mg／m^3。环氧丙烷接触组工人的HP-缬氨酸水平明显高于对照组,差异有极显著性(P=0．0018)。接触组中的每个细胞SCE数明显高于对照组,差异有显著性(P=0．011)。血红蛋白加合物与姐妹染色单体互换的相关系数r为0．762．并且差异有极显著性(P=0．0014)。结论 低浓度环氧丙烷对职业人群具有细胞遗传学毒性。