Genotoxic hazard evaluation in welders occupationally exposed to extremely low-frequency magnetic fields (ELF-MF)

Electric arc welding is known to involve considerable exposure to extremely low-frequency magnetic fields (ELF-MF). A cytogenetic monitoring study was carried out in a group of welders to investigate the genotoxic risk of occupational exposure to ELF-MF. This study assessed individual occupational exposure to ELF-MF using a personal magnetic-field dosimeter, and the cytogenetic effects were examined by comparing micronuclei (MN) and sister chromatid exchange (SCE) frequencies in the lymphocytes of the exposed workers with those of non-exposed control subjects (blood donors) matched for age and smoking habit. Cytogenetic analyses were carried out on 21 workers enrolled from two different welding companies in Central Italy and compared to 21 controls. Some differences between the groups were observed on analysis of SCE and MN, whereas replication indices in the exposed were found not to differ from the controls. In particular, the exposed group showed a significantly higher frequency of MN (group mean ± SEM: 6.10 ± 0.39) compared to the control group (4.45 ± 0.30). Moreover, the increase in MN is associated with a proportional increase in ELF-MF exposure levels with a dose-response relationship. A significant decrease in SCE frequency was observed in exposed subjects (3.73 ± 0.21) compared to controls (4.89 ± 0.12). The hypothesis of a correlation between genotoxic assays and ELF-MF exposure value was partially supported, especially as regards MN assay. Since these results are derived from a small-scale pilot study, a larger scale study should be undertaken.     

Occupational exposure to 50 Hz magnetic fields in workers employed in various jobs

BACKGROUND: Information on occupational exposure to ELF magnetic fields (MF) in workers is largely insufficient, and is mostly based on results obtained in Scandinavian countries and North America. Accordingly, the collection of further data is needed, especially in workers exposed in other countries, including in Italy. METHODS: One hundred and fifty workers (84 males and 66 females) employed in 28 different jobs in the Emilia-Romagna Region of Italy were examined. Individual exposure was measured using personal monitors worn on the hip in a belted pouch during three whole work-shifts (8 hours each) of a normal working week. A sampling interval of 10 seconds was adopted, resulting in the collection of more than 8600 measurements for each worker. The individual Time-Weighted Average (TWA) occupational exposure of workers was calculated as the arithmetic mean of all measurements during each work-shift. Environmental non-occupational exposure was also measured. RESULTS: The 50 degrees percentile of individual TWA in the whole group was 0.15 microT, and the 5 degrees - 95 degrees percentile was respectively 0.02-1.45 microT. Job-related exposure (expressed as the mean of the TWA measured in all workers engaged in that job) was highest in substation electric power plant workers (1.12 microT) and in sewing machine workers (0.84 microT), but was lower than 0.2 microT in more than the 70% of the examined jobs. Considering the geometric mean of individual TWA are 27 out of 28 the jobs inducing an exposure lower than 0.2 microT. The lowest exposure was observed in infant school teachers. A high variability was observed among different workers engaged in the same occupation, mainly in substation electric power plant workers, machine testers and grinders in the engineering industry and in sewing machine workers and quality control in garment production. A marked variability of the pattern of exposure during the work-shift was also observed The overall environmental (non-occupational) exposure was 0.044 microT, and individual exposure was lower than 0.2 microT in about 97% of the examined subjects. Occupational exposure was usually higher and was not correlated with environmental exposure. CONCLUSIONS: The results show that the occupational component of overall exposure must be considered in studies on the biological effects of ELF-MF in populations. The high variability observed among workers engaged in the same occupation and the variability of the pattern of exposure certainly constitute major problems and could be a cause of the scarce coherence of the results of epidemiological studies on biological effects of ELF-MF to date. An improvement in protocols for the evaluation of exposure in workers, including the use of personal monitoring, is certainly needed.     

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.

     

Genotoxic hazard evaluation in welders occupationally exposed to extremely low-frequency magnetic fields (ELF-MF)

Electric arc welding is known to involve considerable exposure to extremely low-frequency magnetic fields (ELF-MF). A cytogenetic monitoring study was carried out in a group of welders to investigate the genotoxic risk of occupational exposure to ELF-MF. This study assessed individual occupational exposure to ELF-MF using a personal magnetic-field dosimeter, and the cytogenetic effects were examined by comparing micronuclei (MN) and sister chromatid exchange (SCE) frequencies in the lymphocytes of the exposed workers with those of non-exposed control subjects (blood donors) matched for age and smoking habit. Cytogenetic analyses were carried out on 21 workers enrolled from two different welding companies in Central Italy and compared to 21 controls. Some differences between the groups were observed on analysis of SCE and MN, whereas replication indices in the exposed were found not to differ from the controls. In particular, the exposed group showed a significantly higher frequency of MN (group mean ± SEM: 6.10 ± 0.39) compared to the control group (4.45 ± 0.30). Moreover, the increase in MN is associated with a proportional increase in ELF-MF exposure levels with a dose-response relationship. A significant decrease in SCE frequency was observed in exposed subjects (3.73 ± 0.21) compared to controls (4.89 ± 0.12). The hypothesis of a correlation between genotoxic assays and ELF-MF exposure value was partially supported, especially as regards MN assay. Since these results are derived from a small-scale pilot study, a larger scale study should be undertaken.     

环氧丙烷对职业接触人群的遗传毒性研究

目的研究长期接触低浓度环氧丙烷（PO）对职业人群的遗传毒性。方法对PO作业现场进行环境监测的同时,采集接触组和对照组工人的血样．对染色体畸变、外周血淋巴细胞微核率、姐妹染色单体交换频率、DNA加合物（1-HP-腺嘌呤）和血红蛋白加合物（HP-缬氨酸）含量进行了检测和分析。结果PO车间两个岗位作业工人PO时间加权平均浓度（TWA）分别为2．6mg／m^3和6．9mg／m^3;PO接触组工人的姐妹染色单体交换频率、DNA加合物、血红蛋白加合物水平高于对照组,差异有非常显著性;染色体畸变、外周血淋巴细胞微核率差异无显著性。结论长期接触低浓度PO对职业人群具有遗传毒性。     

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。     

Biological monitoring the exposure to polycyclic aromatic hydrocarbons of coke oven workers in relation to smoking and genetic polymorphisms for GSTM1 and GSTT1.

Occupational exposure to polycyclic aromatic hydrocarbons (PAH) increases the risk of developing lung cancer. Human exposure is often demonstrated by increased internal levels of PAH metabolites and of markers for early biological effects, like DNA adducts and cytogenetic aberrations.Objective: This study aimed to assess whether the current exposure to PAH of coke oven workers in a Dutch plant induced biological effects, and to determine if these effects are influenced by tobacco smoking and by genetic polymorphisms for the glutathione S-transferase genes GSTM1 and GSTT1.Methods: Urinary 1-hydroxypyrene (1-OHpyr) levels were used to monitor the internal dose, while the internal effective dose was assessed by monitoring PAH-DNA adducts, DNA strand breaks (Comet assay), sister-chromatid exchanges (SCE) and cells with a high frequency of SCE (HFC) in lymphocytes together with micronuclei (MN) in exfoliated urothelial cells.Results: Occupational exposure to PAH resulted in statistically significant increased 1-OHpyr levels (P<0.001), but it did not cause a significant induction of SCE, HFC, MN, DNA strand breaks or DNA adducts. Smoking caused a significant increase of 1-OHpyr (P<0.05), SCE (P<0.001), HFC (P<0.001) and DNA adducts (P<0.05), but not of MN or DNA strand breaks. Following correction for the smoking-related effects, no occupational induction of the effect biomarkers could be discerned. Multi-variate analysis did not show a significant influence of GSTM1 and GSTT1 polymorphisms on any biomarker. Also no significant interactions were observed between the various biomarkers.Conclusion: This study shows that in the examined plant, the occupational exposure to PAH does not result in measurable early biological effects     

Occupational exposures to extremely low frequency magnetic fields and postmenopausal breast cancer

BACKGROUND: The association between occupational exposure to extremely low frequency magnetic fields (ELF-MF) and risk of postmenopausal breast cancer was assessed in a case-control study. METHODS: Breast cancer cases were compared to cancer controls. Interviewers elicited information on risk factors and on lifetime work history. Industrial hygienists assigned to each job average duration of exposure to ELF-MF at four levels of intensities ("none," <0.2 microT; "low," 0.2-<0.5microT; "medium," 0.5-<1microT; "high," > or =1-10microT). Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: A total number of 608 cases and 667 controls participated. Adjusting for accepted breast cancer risk factors, we found an OR of 1.13 for lifetime occupational exposure to ELF-MF at medium or high intensities. Risks were larger for exposures before age 35 (OR = 1.40), and statistically significant for exposures before 35 among cases with progesterone receptor positive tumors (OR = 1.56, 95% CI=1.02-2.39). CONCLUSIONS: There appears to be a small increased risk for breast cancer among postmenopausal women exposed occupationally to ELF-MF.     

Lack of association of δ-aminolevulinic acid dehydratase genotype with cytogenetic damage in lead workers

Objective The objective of this study was to evaluate the correlations of genetic polymorphism of genotypes -aminolevulinic acid dehydratase (ALAD), blood lead levels (BLLs), zinc protoporphyrin (ZPP), sister chromatid exchanges (SCEs), and high SCE frequency cells (HFCs) in lead workers.Methods Three groups of lead workers were included in the study: high lead exposure group (26 workers), low lead exposure group (31 workers) and control group (30 controls who lived in an area uncontaminated by lead). Blood samples were taken from all subjects and analyzed for lead levels, ALAD genotype and SCE levels.Results Occupationally exposed workers had significantly higher BLLs, ZPP and hemoglobin levels than the controls. There were no differences among the three groups regarding percentages of ALAD 1-1 and ALAD 1-2 genotypes, but the ALAD 2-2 genotype was not detected in any of the three groups. There were no significant differences among the three groups for BLLs, ZPP and hemoglobin levels based on ALAD 1-1 and ALAD 1-2. Average SCE values in the high lead exposure group were significantly greater than those in the control group (6.2 vs 5.2 SCEs/cell, P<0.05). HFC analysis revealed a significantly higher HFC percentage (53.9%) in the high lead exposure group than in the low lead exposure group (16.1%) and the control group (10%). There appeared to be an interaction effect on HFC percentages between smoking and lead exposure. When multiple regression analysis was used, the factors that affected SCE levels were lead exposure and smoking, but ALAD genotypes did not have any significant effect.Conclusions A significant association existed between both SCE and HFC levels and lead exposure. However, different ALAD genotypes were not found to be associated with levels of blood lead and ZPP in the three groups.     

Occupational and environmental exposure to extremely low frequency-magnetic fields: a personal monitoring study in a large group of workers in Italy

An inaccurate evaluation of exposure is considered a possible cause for the inadequate conclusiveness of epidemiological research on adverse effects of extremely low frequency-magnetic fields (ELF-MF). The objective of this study is to provide an evaluation of current ELF-MF exposure in workers, the specific contribution of occupational exposure to overall 24-h exposure, and the representativeness of a job exposure matrix (JEM). ELF-MF exposure was monitored in 543 workers for 2 days using personal meters. Time-weighted average (TWA) levels at work, at home and outside the home were calculated. A JEM based on the 1988 International Standard Classification of Occupations (ISCO 88) was created. Median exposure at work, at home and outside the home were 0.14, 0.03 and 0.05 μT, respectively. Occupational exposure accounted for about 60% of 24-h exposure. In the JEM, about 50% of the classified occupations included significantly different individual TWAs. Occupational exposure to ELF-MF appeared low. Median exposure levels at home and outside were 20-28% of the occupational level, giving a minor contribution to overall day-to-day exposure. The frequent occurrence of workers with different TWA included under the same job title highlights the risk of misclassification in epidemiological studies on ELF-MF effects based on JEM.     

Validation of a job-exposure matrix for assessment of utility worker exposure to magnetic fields

The aim of this study was to evaluate a 50-Hz electromagnetic field job-exposure matrix used in epidemiological studies of a nationwide cohort of utility workers in Denmark. We compared a job-exposure matrix that distinguished four categories of exposure to 50-Hz time-weighted average (TWA) magnetic fields: low (< 0.1 microT), medium (0.1-0.29 microT), high (0.3-0.99 microT) and very high (> 1.0 microT) of utility company employees with 196 measurements of 8-h exposure for 129 workers in this industry. The 129 workers were selected from the following five main work environments: generation facilities, transmission lines, distribution lines, substations, and other electrically and non-electrically relates jobs. This study shows that the job-exposure matrix can be expected to introduce misclassification mainly between adjacent categories of exposure. Thus, the distribution of measurements of exposure to 50-Hz magnetic fields was similar for workers in the medium and the high exposure matrix categories. But the two extreme categories satisfactorily separate low and very highly exposed workers. The study shows that epidemiological use of this job-exposure matrix might combine the two intermediate categories of exposure. If the sample size in extreme categories provides enough power, a study in which this job-exposure matrix is used should allow detection of a true association between exposure to 50-Hz magnetic field and disease.     

Within-day variability of magnetic fields among electric utility workers: consequences for measurement strategies

Occupational exposure to 50-Hz magnetic fields was surveyed among electric utility workers to investigate (1) components of exposure variability, (2) patterns of autocorrelation between short-term measurements, and (3) imprecision and misclassification due to short-term measurements. Spot measurements every 10 seconds during 81 working days were analyzed for 42 electric utility workers from 10 occupational subgroups and during 8 working days for 4 office workers from the same company. For the 8-hour time-weighted average (TWA) magnetic fields, the variability was partitioned into its components: within workers, between workers, and between groups. For spot measurements of magnetic fields, the within-day variance component also was examined. Autocorrelation functions were determined and numbers of short-term measurements necessary for reliable estimates of 8-hour TWA magnetic fields were assessed. Spot measurements of magnetic fields, as well as 8-hour TWA magnetic fields, were approximately log normally distributed among workers. The mean exposure to magnetic fields was 0.47 microT (n = 81 days) in electric utility workers and 0.12 microT (n = 8 days) in office workers. A large fraction, 76% of the spot measurements total variance, could be attributed to variability within days. For the 8-hour TWA magnetic fields, between-group variability was small and of the same magnitude as between-worker variability. Significant autocorrelations between short-term averages of 7.5, 15, and 30 minutes were present, when taken within periods of 30 minutes. One-hour averages showed no autocorrelation. Simulations showed that, due to high within-day variability and autocorrelation, a limited number of short-term measurements of magnetic fields in electric utility workers are likely to result in imprecise estimates of 8-hour TWA magnetic fields. Measurement strategies relying on short-term (spot) measurements are therefore likely to result in misclassification of exposure and consequently absent or spurious exposure-response relations.     

Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents

We examined sister chromatid exchanges (SCEs) and micronuclei (MN; cytokinesis-block method) in cultured peripheral lymphocytes from 52 female workers of two shoe factories and from 36 unexposed age- and sex-matched referents. The factory workers showed an elevated level of urinary hippuric acid, a biomarker of toluene exposure, and workplace air contained high concentrations of various organic solvents such as toluene, gasoline, acetone, and (in one of the plants only) ethylacetate and methylenediphenyl diisocyanate. The shoe factory workers showed a statistically significant higher frequency of micronucleated binucleate lymphocytes in comparison with the referents. This finding agreed with three preliminary MN determinations (each comprising 27-32 shoe workers and 16-20 controls) performed in one of the plants 2-5 years earlier. The shoe factory workers also had a lower average level of blood hemoglobin than the referents. In contrast, no difference was found between the groups in SCE analysis. Smokers showed significantly higher mean frequencies of SCEs per cell and high frequency cells (HFC) than nonsmokers. Aging was associated with increased MN rates and reduced cell proliferation. Polymorphism of the glutathione S-transferase M1 gene (GSTM1) did not affect the individual level of SCEs; but in smoking shoe workers an effect of the occupational exposure on the frequency of micronucleated cells could be seen only in GSTM1 null subjects. The low prevalence of the glutathione S-transferase T1 (GSTT1) null genotype precluded the evaluation of the influence of GSTT1 polymorphism. Our results show that the shoe factory workers have experienced genotoxic exposure, which is manifest as an increase in the frequency of MN, but not of SCEs, in peripheral lymphocytes. The exposures responsible for the MN induction could not be identified with certainty, but exposure to benzene in gasoline and methylenediphenyl diisocyanate may explain some of the findings.     

Exposure to extremely low frequency magnetic fields among working women and homemakers.

Given concerns with potential health effects of exposure to magnetic fields, the goal of this study was to examine the magnitude and sources of occupational and residential exposure to extremely low frequency (primarily 60 Hz) magnetic fields among women. Exposure to 60 Hz magnetic fields was surveyed among cases and controls recruited for a study of breast cancer in 25 counties in North Carolina. The 273 women who participated wore an integrating personal magnetic-field exposure meter (AMEX 3-D) that measured their time-weighted average (TWA) exposure. A questionnaire was administered to determine the duration and frequency of electric appliance and machinery use. The geometric mean (GM) of the TWA exposure for employed women was 0.138 microT (range 0.022-3.636 microT) and for homemakers 0.113 microT (range 0.022-0.403 microT). Women working in manufacturing and industrial facilities had the highest exposure (GM 0.265 microT, range 0.054-3.436 microT), while nurses and health technicians (GM 0.134 microT, range 0.032-0.285 microT) and teachers and school administrators (GM 0.099 microT, range 0.035-0.673 microT) had the lowest exposures. Job titles, unless very limited in scope and/or environment, self-reported information about equipment use, potential exposure sources, time, and distance were not good predictors of magnetic-field exposure. Furthermore, the results show that occupations previously observed to have increased risk of breast cancer, such as teachers, nurses, administrative support, and housewives, did not have elevated average magnetic field exposures. Therefore, it is questionable whether exposure to power frequency magnetic fields is the cause of the increased breast cancer risk seen in these occupations.     

Genotoxicity evaluation in workers occupationally exposed to lead

Lead (Pb) is a widely used heavy metal with a broad industrial usage. Nevertheless, Pb is a serious public health issue as it is one of the most widespread environmental and industrial toxins. The aim of this investigation was to assess the genotoxicity of Pb using the comet assay, micronucleus (MN) and chromosomal aberrations (CA) test. Blood and urinary Pb content, levels of δ-aminolevulinic acid dehydratase in the erythrocytes (E-ALAD) and δ-aminolevulinic acid in urine (U-ALA) were determined. The exposure associated oxidative stress was also studied. The study group comprised of 90 male Pb recovery unit workers and 90 matched controls. The results indicated that the exposed workers had a significantly higher mean comet tail length than that of controls (P<0.05). Analysis of micronuclei in buccal epithelial cells (BEC’s) and peripheral blood lymphocytes (PBL) revealed that there was a significant increase in frequency of MN in exposed subjects than controls. The frequency of aberrant metaphases was also found to be significantly elevated in the Pb exposed workers. The levels of antioxidant enzymes were relatively reduced (P>0.05) while the rate of lipid peroxidation was higher in the exposed subjects. Blood and urinary Pb concentrations were found to be higher in exposed workers than in controls. E-ALAD levels were reduced and U-ALA levels were elevated in the exposed subjects in comparison to controls. Results of analysis, taking the confounding factors into consideration provide evidence for the association of Pb exposure and genotoxicity, and predict the increased risk of cancer to the exposed workers. In view of the observed results, it can be strongly concluded that the workers comprise the risk group and adequate safety, precautionary and preventive measures could only minimize exposure and the related health hazards.     

Cytogenetic tests performed on operating room personnel (the use of anaesthetic gases)

Objectives: Personnel exposure to anaesthetic gases in the health sector, whether in the operating room, recovery room, or in the context of outpatient clinics, may entail a health risk. The goal of this research was to study the cytogenetic effects of chronic exposure to small doses of pollutants in operating theatres. Methods: Results of cytogenetic analyses [structural chromosomal aberrations (SCAs), sister chromatid exchange (SCE) and micronucleus (MN) test] of anaesthetists and other personnel handling anaesthetic gases, who only occasionally work in zones of ionizing radiation, were compared with results from radiologists, occupationally exposed to ionizing radiation only, and with the results obtained from a group of Slovene citizens who were never exposed to genotoxic agents. Results: This study involved 153 workers handling anaesthetic gases. The average frequency of SCAs in the group working with anaesthesia was 2.693. The result was statistically significantly higher than in the group of radiologists and Slovene citizens. The frequency of SCE and MN was also statistically significant. A number of authors, who used the same cytogenetic tests, found similar results in the group of anaesthetist. Conclusion: The results of our study indicate that exposure to anaesthetic gases induced changes in human chromosomes.     

Assessment of occupational genotoxic risk in the production of rubber tyres

A broad spectrum of substances is used in the rubber industry, many of them being genotoxic and/or carcinogenic. Convincing evidence of an excess of certain forms of cancer among rubber workers has been provided. The objective of this study was to determine the genotoxic effects in a group of individuals engaged in the production of rubber tyres from a Portuguese factory. Peripheral blood samples were collected from 32 exposed workers and 32 controls, and micronucleus (MN) test, sister chromatid exchanges (SCE) and comet assay were performed. Urinary thioethers were measured as a general biomarker of exposure to electrophilic compounds, and genetic polymorphisms in metabolizing enzymes (CYP2E1 Dra I, EPHX1 codons 113 and 139, GSTP1 codon 105, and GSTM1 and GSTT1 deletion polymorphisms) were analysed as susceptibility biomarkers. Excretion of thioethers was found significantly higher in rubber workers. Also, a non-significant increase in MN frequency related to time of exposure and no effect in SCE were observed in the exposed. Comet assay data showed decreased TL values in the exposed population with respect to the control group, this might indicate the induction of crosslinks by the substances present in the workplace environment. Significant increase in MN frequency was obtained for GSTT1 null exposed individuals with respect to positive ones, and interaction with GSTP1 polymorphism was found. Higher levels of cytogenetic test frequencies were observed in epoxide hydrolase expected low activity donors with respect to medium and high activity individuals. No effect of CYP2E1 or GSTM1 variants was obtained in the biomarkers analysed.     

异佛尔酮二异氰酸酯毒理学研究

经ＧＰＭＴ法检测，２５％异佛尔酮二异氰酸酯（ＩＰＤＩ）对豚鼠的致敏率为５０％，属中等致敏物。ＩＰＤＩ对小鼠脾脏抗体生成细胞有抑制作用，但可刺激豚鼠Ｔ淋巴细胞及淋巴细胞转化功能。Ａｍｅｓ试验阴性，１６６ｍｇ／ｋｇＩＰＤＩ可诱导大鼠骨髓染色体畸变、小鼠骨髓嗜多染红细胞微核率增高、小鼠骨髓细胞ＳＣＥ增加及ＵＤＳ试验阳性。ＩＰＤＩ５３～４２４ｍｇ／Ｌ对小鼠骨髓细胞ＤＮＡ合成有明显抑制作用，表明ＩＰＤＩ对体细胞具有断裂剂活性和损伤ＤＮＡ作用。小鼠精子畸形试验和睾丸染色体畸变试验表明对生殖细胞无明显损伤作用。大鼠致畸试验说明ＩＰＤＩ为不致畸物。职业接触ＩＰＤＩ人群调查表明，接触者有明显的粘膜和呼吸道刺激症状，高浓度接触者肺功能（ＦＶＣ、ＦＥＶ１．０）较对照组有下降趋势，其他心、肝、肾功能、外周血淋巴细胞亚群检查、染色体畸变分析、内科、神经系统检查均与对照组无显著性差异。     

The usefulness of cytogenetic biomarkers as intermediate endpoints in carcinogenesis.

During the last decades, cytogenetic biomarkers in peripheral lymphocytes have been used to assess exposure to carcinogenic or mutagenic agents in occupational settings. The first method in use assessed chromosomal aberrations (CA). It is generally accepted that chromosomal mutations are causal events in the development of neoplasia, and it has earlier been postulated, but not proven, that increased chromosomal damage may reflect an enhanced cancer risk. Two less laborious techniques, sister chromatoid exchanges (SCE) and micronuclei (MN), were introduced later-on in occupational health surveillances. SCE represent symmetrical exchanges between sister chromatids; generally they do not result in alteration of the chromosome morphology. MN represent small, additional nuclei formed by the exclusion of chromosome fragments or whole chromosomes lagging at mitosis. MN rates therefore indirectly reflect chromosome breakage or impairment of the mitotic apparatus. The health significance of increased levels of SCE and MN is poorly understood. The usefulness of these cytogenetic techniques for implementing preventive measures in the workplaces depend on how well they serve as biomarkers of exposure but also on whether they can predict cancer risk or not. Recently performed epidemiological studies show that the CA frequency predicts the overall cancer risk in healthy subjects. Such associations could not been seen for SCE or MN. Age, sex, or time since test did not affect the predictive value of CA. This predictivity was seen irrespective of whether the subjects had been smokers or occupationally exposed to carcinogenic agents. Risk factors such as age, smoking and occupational exposures usually explain only some of the interindividual variation in CA frequency. It seems reasonable that not yet identified individual susceptibility factors explain a large fraction of the interindividual CA variation and also the cancer predictivity of the CA biomarker.     

Differential induction of micronuclei in peripheral lymphocytes and exfoliated urothelial cells of workers exposed to 4,4'-methylenebis-(2-chloroaniline) (MOCA) and bitumen fumes

Cytogenetic end-points used to estimate risk of genotoxic events in workers include the measurement of micronuclei (MN) in exfoliated cells, lymphocytes, and other tissues. Micronuclei are chromatin-containing bodies outside the cell nucleus resulting from contaminant-induced DNA damage. A review of 71 reports of human genotoxic responses to chemical or physical agents published between 1999 and 2001 revealed that 14% of such studies measured genotoxicity endpoints in specific target tissues relevant to the site of disease for the agent examined; 18% used endpoints in surrogate or non-target tissues but considered the relations between endpoints in surrogate and disease target tissues, and 68% measured genotoxicity endpoints in accessible tissues without reference to specific targets for disease. Methylenebis-(2-chloroaniline) (MOCA), used in polyurethane manufacture, is a suspected bladder carcinogen. Bitumen, used in road surfacing, contains skin and lung carcinogens. In this study, we aimed to compare genotoxicity in urothelial cells and in lymphocytes of workers exposed to these materials. Twelve men employed in polyurethane manufacture, twelve bitumen road layers, and eighteen hospital stores personnel (controls) were recruited and all provided blood and urine samples on the same day. Blood cultures were prepared using a cytochalasin B-block method. Exfoliated urothelial cells were collected from urine and stained for light microscopy. The number of MN in urothelial cells was higher in MOCA-exposed (14.27 +/- 0.56 MN/1000, 9.69 +/- 0.32 MN cells/1000) than in bitumen exposed workers (11.99 +/- 0.65 MN/1000, 8.66 +/- 0.46 MN cells/1000) or in control subjects (6.88 +/- 0.18 MN/1000, 5.17 +/- 0.11 MN cells/1000). Conversely, in lymphocytes, MN were higher in bitumen-exposed (16.24 +/- 0.63 MN/1000, 10.65 +/- 0.24 MN cells/1000) than in MOCA-exposed workers (13.25 +/- 0.48 MN/1000, 8.54 +/- 0.14 MN cells/1000) or in control subjects (9.24 +/- 0.29 MN/ 1000, 5.93 +/- 0.13 MN cells/1000). The results of this study suggest that genotoxins can cause different rates of micronuclei formation in different tissues. Thus, the sensitivity and relevance to cancer risk may be greater if the tissues selected for genotoxicity studies reflect the target tissue for the chemicals concerned.